The development of anti-glomerular basement membrane nephritis in two children with Alport's syndrome after renal transplantation: characterization of the antibody target

Two children with Alport's syndrome are described, who developed anti-glomerular basement membrane (GBM) antibody-mediated nephritis after renal transplantation. The reactivity of antibodies in their serum with collagenase-solubilized normal GBM was examined by SDS-PAGE with one- and two-dimensional immunoblotting. The specificity was compared with that of antibodies present in serum from a patient with Goodpasture's syndrome, and a mouse monoclonal antibody (MCA-P1), directed against the Goodpasture antigen. All reacted in a similar way with collagenase-solubilized GBM. Since abnormalities in the composition of the GBM are present in Alport's syndrome, it is proposed that differing antigen composition of GBM in the host compared with the donor kidney, together with transplant rejection, may have provoked the development of post-transplant anti-GBM antibodies.     

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.     

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。     

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.     

成年人肾小球基底膜厚度及基底膜变薄标准研究

Objective To elucidate the thickness of glomerular basement membrane (CBM) in adult kidney tissue and to establish the standard of GBM thickness for thin basement membrane nephropathy (TBMN) in China. Methods Kidney cortex tissue samples apart from cancer focus were collected from 29 patients undergoing nephrectomy. Clinical data of patients were analyzed. Light, immunofluorescence and electron microscope examinations were performed on these 29 samples to measure the thickness of GBM and the distribution of collagen Ⅳα3, α5 chains. Results There were fifteen male and fourteen female cases with age (55.9±14.9) (20-80) years old. No familial history of renal disease or other diseases was found in these cases. The CBM thickness of these samples was (363.6 ±46.8) nm, which was associated with gender. GBM thickness was (384.0±41.7) nm in male, and (335.0±39.2) nm in female, which was significantly different (P=0.008). The standard to diagnose thin GBM should be the mean minus double standard deviation. So the standard of GBM thickness for TBMN should be <270 nm. Conclusions The GBM thickness of adults is (363.6±46.8) nm. GBM thickness is associated with gender, which is thicker in males with significant difference. It is suggested that the standard of GBM thickness for TBMN in adult should be <270 nm, and the difference of GBM thickness between male and female should be considered too.     

成年人肾小球基底膜厚度及基底膜变薄标准研究

Objective To elucidate the thickness of glomerular basement membrane (CBM) in adult kidney tissue and to establish the standard of GBM thickness for thin basement membrane nephropathy (TBMN) in China. Methods Kidney cortex tissue samples apart from cancer focus were collected from 29 patients undergoing nephrectomy. Clinical data of patients were analyzed. Light, immunofluorescence and electron microscope examinations were performed on these 29 samples to measure the thickness of GBM and the distribution of collagen Ⅳα3, α5 chains. Results There were fifteen male and fourteen female cases with age (55.9±14.9) (20-80) years old. No familial history of renal disease or other diseases was found in these cases. The CBM thickness of these samples was (363.6 ±46.8) nm, which was associated with gender. GBM thickness was (384.0±41.7) nm in male, and (335.0±39.2) nm in female, which was significantly different (P=0.008). The standard to diagnose thin GBM should be the mean minus double standard deviation. So the standard of GBM thickness for TBMN should be <270 nm. Conclusions The GBM thickness of adults is (363.6±46.8) nm. GBM thickness is associated with gender, which is thicker in males with significant difference. It is suggested that the standard of GBM thickness for TBMN in adult should be <270 nm, and the difference of GBM thickness between male and female should be considered too.     

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。     

Hereditary disorders of the glomerular basement membrane

Increased knowledge of the biochemical composition of the glomerular basement membrane (GBM) and the introduction of molecular genetics has shed new light on the hereditary disorders of the GBM. In this review three disorders are highlighted. About 85% of the cases reported as Alport syndrome are transmitted as the X-linked form and are due to mutations of the COl4A5 chain localized at Xq22. The autosomal recessive form can be explained by mutations in the COl4A3 and COl4A4 gene. Anti-GBM nephritis leading to loss of the renal allograft in about 1% – 5% of transplanted Alport patients can be the tragic consequence of this disorder. Some patients with familial benign hematuria have an abnormality of COl4A4. The nail-patella syndrome is a rare autosomal dominant disorder defined by the association of nail dysplasia, bone abnormalities, and frequently renal disease. The gene is localized in region 9q34.1, COl5A1 is not involved. The Finnish type is the best known of the different forms of congenital nephrotic syndrome. The gene has been mapped to the long arm of chromosome 19. Diffuse mesangial sclerosis occurs in the isolated form and as part of the Denys Drash syndrome. Disturbances of the WT1 function in the epithelial cells can have a role in the renal abnormalities of the Denys Drash syndrome. Received May 7, 1996; accepted May 21, 1996     

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.     

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。     

Membranous nephropathy with anti-tubular basement membrane antibody may be X-linked

The association of membranous nephropathy with Fanconi syndrome and anti-tubular basement antibodies appears to be a distinct subset of familial membranous nephropathy. We studied two Chinese families with four affected boys to evaluate the mode of inheritance of disease. HLA haplotype analysis of the family members in these two pedigrees did not reveal any significant linkages. However, microsatellite analysis of both pedigrees using markers on the X chromosome suggested linkage to the long arm of the X chromosome between the microsatellite markers DXS1001 and DXS1227. Identification and analysis of additional pedigrees may allow more precise mapping of the disease gene for anti-tubular basement membrane antibody-associated membranous nephropathy. Received: 29 April 1999 / Revised: 6 October 1999 / Accepted: 6 October 1999     

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.     

Increased glucose increases glomerular basement membrane in metanephric culture

A model of in vitro renal development has been used to examine the effect of glucose on the glomerular basement membrane. Glomerular differentiation in this system progresses to an arborizing tuft of podocytes overlying well-formed basal lamina. The proportional amount of lamina densa and dense fibrillary matrix was increased in blastemas grown in an increased amount of glucose during the last 4 of 7 days in culture. These observations indicate that glucose itself can stimulate an accumulation of basement membrane, an excess of which is characteristic of diabetic microangiopathy.     

A histopathological study on the prognosis of childhood IgA nephropathy and glomerular basement membrane lesions

Seventy-three patients with IgA nephropathy (IgAGN), under the age of 15 years at the time of the discovery of the disease, were investigated with respect to glomerular basement membrane (GBM) lesions. Irregular attenuation or widening of GBM, especially on the epithelial side, was observed in 28 cases (38%). These two changes are referred to aslysis of GBM and were considered to be the primary and specific changes among the GBM lesions in IgAGN. GBM thickening with layering of lamina densa was found in 37 of 73 cases (51%), but this change has been observed in other types of glomerular diseases. GBM lesions similar to those seen in IgAGN were also observed in Henoch-Schönlein purpura nephritis (HSPN) and poststreptococcal acute glomerulonephritis (PSAGN). Lysis of GBM was observed only in IgAGN, HSPN and PSAGN. Subepithelial and intramembranous deposits appeared to have an important role in the development of these GBM lesions. The presence of GBM lesions was correlated with a high incidence of cellular crescents but not with other clinical or light microscopic findings. The presence of these GBM lesions in IgAGN does not have a significant effect on the prognosis, at least in childhood. The affected GBM seemed to recover without leaving any significant residual damage in most cases. In the long-term prognosis of the disease non-immunological factors, such as ageing or hypertension, seem to be important.     

Thin basement membrane nephropathy associated with minimal change disease in a 15-year-old boy

Thin basement membrane nephropathy (TBMN) is characterized clinically by persistent hematuria, minimal proteinuria, normal renal function, another family member with hematuria, and a benign course. Especially in childhood TBMN, proteinuria of any degree is reported to be uncommon. We report on a boy with benign familial hematuria found by urinary screening at 3 years of age who presented with nephrotic syndrome (NS) at 15 years of age. His renal histology showed TBMN associated with minimal change disease (MCD). Treatment with corticosteroid resulted in complete remission of NS in a short period of time, while isolated hematuria persisted during the follow-up period despite this therapy. We speculate, therefore, that the nephrotic range proteinuria is not due to TBMN but rather is the manifestation of associated MCD. Several cases of TBMN with NS have been reported in adults, but it has not yet been reported in children in the literature. To our knowledge, this is the first case of childhood TBMN associated with NS resulting from coincidental MCD.     

Morphometric study of glomerular basement membrane and proximal tubular basement membrane in adult thin basement membrane disease

Background. Thin basement membrane disease (TBMD) is a benign hereditary glomerulopathy with a diffuse attenuation of glomerular basement membrane (GBM). Whether the development of renal basement membranes other than GBM is normal in TBMD has not yet been resolved. Methods. We performed a morphometric study to measure the thickness of GBM and proximal tubular basement membrane (P-TBM) in 44 adult patients with TBMD and in 10 adult diseased controls confirmed to have minor glomerular abnormalities. Results. There was a significant difference between the patients with TBMD and the diseased controls in the thickness of the GBM; however, there was no significant difference between the two groups in the thickness of the P-TBM. In the patients with TBMD, the thickness of the GBM was unchanged with age, but the thickness of the P-TBM increased with age, as did that in the diseased controls. Conclusion. Our morphometric study clarified that the development of P-TBM was normal in the patients with TBMD. Received: October 7, 1998 / Accepted: May 27, 1999     

Thin basement membrane nephropathy cannot be diagnosed reliably in deparaffinized, formalin-fixed tissue.

In diagnostic renal pathology, electron microscopy is ideally performed on glutaraldehyde-fixed, plastic resin-embedded tissue (EM-G). When no glomeruli are present in the portion of the biopsy fixed in glutaraldehyde, formalin-fixed, paraffin-embedded tissue can be reprocessed for electron microscopy (EM-F). The usefulness of this salvage technique for the diagnosis of thin basement membrane nephropathy (TBMN) has not been studied systematically. Here we compare the glomerular basement membrane (GBM) thickness by EM-G vs EM-F in 21 renal biopsies, including TBMN (eight patients), normals (two patients), minimal change disease (MCD) (six patients) and diabetic nephropathy (DN) (five patients). There was significant reduction of the GBM thickness by EM-F compared with EM-G across all diagnostic categories in all 21 cases. The mean percentage reduction in GBM thickness was 23% for the TBMN cases, 40% for the normal/MCD cases and 34% for the DN cases. Four patients with MCD had a mean GBM thickness by EM-F that fell below the defining threshold for diagnosis of TBMN. For the TBMN cases, the 99th percentile for GBM thickness by EM-F was 194 nm, suggesting that the diagnosis of TBMN by EM-F can be excluded with confidence if the GBM thickness is above 200 nm. No clear criteria could be established to diagnose TBMN by EM-F. Renal pathologists should be aware that reprocessing of paraffin tissue for EM causes artifactual GBM thinning that precludes accurate diagnosis of TBMN.     

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.     

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.