Segmentation and Analysis of the Glomerular Basement Membrane in Renal Biopsy Samples Using Active Contours: A Pilot Study

We report a case of nail-patella syndrome (NPS) with unusual thinning of the glomerular basement membrane (GBM) associated with a novel heterozygous variant in the LMX1B gene. A 43-year-old female patient with a previous diagnosis of NPS, referred to our hospital for persistent proteinuria, underwent a renal biopsy, which revealed minor glomerular abnormalities. She underwent a second renal biopsy at the age of 56 owing to the presence of persistent proteinuria and decline in serum albumin, meeting the diagnostic criteria for nephrotic syndrome. Light microscopy demonstrated glomerulosclerosis and cystic dilatation of the renal tubules. Notably, electron microscopy revealed unusual thinning of the GBM, which is quite different from typical biopsy findings observed in patients with NPS, characterized by thick GBM with fibrillary material and electron-lucent structures. Comprehensive genetic screening for 168 known genes responsible for inherited kidney diseases using a next-generation sequencing panel identified a novel heterozygous in-frame deletion-insertion (c.723_729delinsCAAC: p.[Ser242_Lys243delinsAsn]) in exon 4 of the LMX1B gene, which may account for the disrupted GBM structure. Further studies are warranted to elucidate the complex genotype-phenotype relationship between LMX1B and proper GBM morphogenesis.

Download Full-text

Monotypic IgG1-kappa Atypical Anti-Glomerular Basement Membrane Nephritis: A Case Report

Case Reports in Nephrology and Dialysis ◽

10.1159/000498844 ◽

2019 ◽

Vol 9 (1) ◽

pp. 8-14

Author(s):

Maxim Olivier ◽

Harold Watson ◽

Danielle Lee ◽

Viresh Mohanlal ◽

Mario Madruga ◽

...

Keyword(s):

Mycophenolate Mofetil ◽

Basement Membrane ◽

Renal Biopsy ◽

Glomerular Basement Membrane ◽

Hemorrhagic Cystitis ◽

Oral Cyclophosphamide ◽

First Line ◽

Circulating Autoantibodies ◽

Line Drug ◽

Observation Period

Anti-glomerular basement membrane (anti-GBM) glomerulonephritis is a rare disease caused by autoantibodies against the glomerular basement membrane. Atypical anti-GBM nephritis is clinically less aggressive and characterized by the absence of circulating autoantibodies to the basement membrane. A previously healthy 53-year-old white woman presented with a rising creatinine over a short observation period. Renal biopsy, urinary sediment, and laboratory testing confirmed the diagnosis of atypical anti-GBM disease. She received plasmapheresis, steroids, and cyclophosphamide. She developed hemorrhagic cystitis early in the treatment from oral cyclophosphamide and mycophenolate mofetil was substituted as a first-line drug. She responded favorably and continued on mycophenolate mofetil without evidence of relapse. Despite the absence of circulating autoantibodies, a diagnosis of atypical anti-GBM nephritis should not be excluded if a high index of clinical suspicion exists. Early renal biopsy should be considered. Mycophenolate mofetil may be a reasonable replacement for oral cyclophosphamide in the treatment of atypical anti-GBM disease when cyclophosphamide is contraindicated.

Download Full-text

Alport Syndrome and Thin Glomerular Basement Membrane Nephropathy: A Practical Approach to Diagnosis

Archives of Pathology & Laboratory Medicine ◽

10.5858/133.2.224 ◽

2009 ◽

Vol 133 (2) ◽

pp. 224-232 ◽

Cited By ~ 2

Author(s):

Mark Haas

Keyword(s):

Electron Microscopy ◽

Basement Membrane ◽

Renal Biopsy ◽

Glomerular Basement Membrane ◽

Alport Syndrome ◽

Autosomal Recessive ◽

Type Iv Collagen ◽

The Past ◽

Type Iv ◽

Pathologic Features

Abstract Context.—Alport syndrome and thin glomerular basement membrane nephropathy (TBMN) are genetically heterogenous conditions characterized by structural abnormalities in the glomerular basement membrane and an initial presentation that usually involves hematuria. Approximately 40% of patients with TBMN are heterozygous carriers for autosomal recessive Alport syndrome, with mutations at the genetic locus encoding type IV collagen α3 [α3(IV)] and α4 chains. However, although the clinical course of TBMN is usually benign, Alport syndrome, particularly the X-linked form with mutations in the locus encoding the α5 chain of type IV collagen [α5(IV)], typically results in end-stage renal disease. Electron microscopy is essential to diagnosis of TBMN and Alport syndrome on renal biopsy, although electron microscopy alone is of limited value in distinguishing between TBMN, the heterozygous carrier state of X-linked Alport syndrome, autosomal recessive Alport syndrome, and even early stages of X-linked Alport syndrome. Objectives.—To review diagnostic pathologic features of each of the above conditions, emphasizing the need for immunohistology for α3(IV) and α5(IV) in addition to electron microscopy to resolve this differential diagnosis on a renal biopsy. The diagnostic value of immunofluorescence studies for α5(IV) on a skin biopsy in family members of patients with Alport syndrome also is reviewed. Data Sources.—Original and comprehensive review articles on the diagnosis of Alport syndrome and TBMN from the past 35 years, primarily the past 2 decades, and experience in our own renal pathology laboratory. Conclusions.—Although Alport syndrome variants and TBMN do not show characteristic light microscopic findings and can be difficult to differentiate from each other even by electron microscopy, using a combination of electron microscopy and immunohistology for α3(IV) and α5(IV) enables pathologists to definitively diagnose these disorders on renal biopsy in most cases.

Download Full-text

Thin glomerular basement membrane nephropathy and other collagenopathies

10.1093/med/9780199592548.003.0325_update_001 ◽

2018 ◽

Author(s):

Laurence Heidet ◽

Bertrand Knebelmann ◽

Marie Claire Gubler

Keyword(s):

Basement Membrane ◽

Renal Disease ◽

Renal Biopsy ◽

Glomerular Basement Membrane ◽

Alport Syndrome ◽

Autosomal Dominant ◽

Increased Risk ◽

Autosomal Dominant Fashion ◽

Nail Patella Syndrome

The discovery of a thin glomerular basement membrane in a renal biopsy without any other abnormalities can be explained in a number of ways. This could be an early biopsy in a patient with Alport syndrome, or it could be an individual who is a carrier for an Alport gene. These carriers are at increased risk of significant renal disease in their lifetime and some have proteinuria as well as haematuria, so they can no longer be equated with the historic label of benign familial haematuria. Some families with a thin glomerular basement membrane and haematuria inherited in an autosomal dominant fashion do not appear to have linkage to COL4 genes. Others have variable renal disease that has sometimes given rise to a label of mild but autosomal dominant Alport syndrome. This territory might also attract the label basement membrane 345 collagenopathy. Other uncommon conditions affecting the glomerular basement membrane include nail patella syndrome.

Download Full-text

Anti-Glomerular Basement Membrane Antibody Disease with Granulomatous Lesions on Renal Biopsy

Internal Medicine ◽

10.2169/internalmedicine.46.6160 ◽

2007 ◽

Vol 46 (6) ◽

pp. 295-301

Author(s):

Masaki Takahashi ◽

Shigeru Otsubo ◽

Takashi Takei ◽

Hidekazu Sugiura ◽

Kazuhiko Yoshida ◽

...

Keyword(s):

Basement Membrane ◽

Renal Biopsy ◽

Glomerular Basement Membrane ◽

Granulomatous Lesions

Download Full-text

P0481MORTALITY PREDICTORS IN ANCA-ASSOCIATED VASCULITIS AND ANTI-GLOMERULAR BASEMENT MEMBRANE DISEASE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0481 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Filipa Cardoso ◽

Maria Do Mar Menezes ◽

Miguel Bigotte Vieira ◽

Mário Góis ◽

Helena Viana ◽

...

Keyword(s):

Blood Pressure ◽

Basement Membrane ◽

Serum Creatinine ◽

Renal Biopsy ◽

Diastolic Blood Pressure ◽

Glomerular Basement Membrane ◽

Categorical Variables ◽

Infectious Episode ◽

Pulmonary Manifestations

Abstract Background and Aims The antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and anti-glomerular basement membrane (GBM) disease are autoimmune diseases that cause necrotizing crescentic glomerulonephritis. These diseases portend an increased risk of end-stage kidney disease and death. The main objective of our study was to identify predictors of mortality in patients with these diseases. Method Retrospective analysis of patients diagnosed with AAV and anti-GBM disease by renal biopsy performed between 2013 and 2019. The minimum duration of follow-up was 6 months. Demographic, laboratory and histological characteristics were studied. The primary endpoint was death due to any cause. Continuous variables were presented as means or medians, according to normality and categorical variables presented as frequencies. The comparison between subgroups of patients was performed using the Wilcoxon, Fisher exact test or t-test, chi-square test, according to normality. Univariate and multivariate logistic regression models were fitted to identify variables associated with death. STATA 14.2 statistical package was used and p < 0.05 was considered statistically significant. Results We identified 40 patients, 37 (95%) were caucasian and 22 (55%) female. The mean age was 69 years, serum creatinine 3.4 (2.3 – 4.5) mg/dL, eGFR 14 (11-23) ml/min/1.73 m2 and proteinuria 1.42 (0.75 – 3.38) g/day. Twenty-seven (68%) had a past medical history of hypertension and 3 (8%) type two diabetes. Thirty-three (83%) presented with constitutional symptoms and 12 (30%) had pulmonary manifestations, while the other manifestations were less frequent. The average time between symptoms presentation and therapy initiation was 119 days. Mean follow-up was 1094 days. Renal biopsy showed grade 0 interstitial fibrosis and tubular atrophy in 5 patients (13%), grade 1 in 13 (33%), grade 2 in 8 (20%) and grade 3 in 14 (35%). The majority had no vessel involvement (24, 60%) and grade 2 acute tubular necrosis (18, 45%). Inflammatory infiltrate was present in 25 patients (63%). At 6 and 12 months, 15 (38%) and 9 (23%) were dialysis dependent, respectively. All patients were treated with prednisolone, 14 (35%) with cyclophosphamide, 15 (38%) with rituximab and 14 (35%) underwent plasmapheresis. Eighteen (45%) patients were maintained on azathioprine. At the end of follow-up, 13 patients had died and 2 relapses occurred. Eleven (46%) patients presented at least one serious infectious episode. Older age (OR 1.10, 95% [1.01-1.20], p=0.035), higher diastolic blood pressure (OR 1.09, 95% [1.00-1.12], p=0.046), and lower C3 levels (OR 0.003, 95% [0.000-0.525], p=0.027) were associated with higher mortality on univariate analysis. On multivariate analysis, only higher diastolic blood pressure remained significant. Pathology findings and serum creatinine values were not associated with higher mortality Conclusion Overall mortality in AAV and anti-GBM has decreased over the last two decades with the use of immunosuppressive therapies. However, mortality rates remain high and most deaths occur during the first year following diagnosis. Early detection of infections with prompt initiation of treatment may help to reduce mortality. Additionally, the identification of risk factors associated with a higher risk of mortality and that could allow individualization of therapy remains a challenge.

Download Full-text

Clinical and immunologic characteristics of Japanese patients with anti-glomerular basement membrane disease: case reports and literature review

Renal Replacement Therapy ◽

10.1186/s41100-021-00317-z ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Yoshinosuke Shimamura ◽

Takuto Maeda ◽

Koki Abe ◽

Yayoi Ogawa ◽

Hideki Takizawa

Keyword(s):

Basement Membrane ◽

Serum Creatinine ◽

Renal Biopsy ◽

Glomerular Basement Membrane ◽

Medical Center ◽

Case Reports ◽

Oral Prednisolone ◽

Japanese Patients ◽

Disease Case ◽

Old Japanese

Abstract Background Clinical studies of anti-glomerular basement membrane (GBM) disease were limited because of the low incidence. We aimed to report the characteristics, treatments, and outcomes of patients with anti-GBM disease at a tertiary reference medical center in Japan and review the literature of mortality in patients with anti-GBM disease. Case presentation Case 1 was a 72-year-old Japanese man that was referred with worsening of the serum creatinine (from 1.1 to 27.3 mg/dL). Anti-GBM disease was confirmed by renal biopsy, and treatments with oral prednisolone and plasmapheresis were initiated. Although his anti-GBM antibody decreased (from 476 to 18 units/mL) after the treatments, the patient died from lung abscess. Case 2 was a 32-year-old Japanese man that presented with fever and macroscopic hematuria. At presentation, his serum creatinine was 4.2 mg/dL, and anti-GBM antibody was 265 units/mL. Renal biopsy confirmed the diagnosis of anti-GBM disease, and intensive treatments with plasmapheresis and methyl prednisolone were started, followed by oral prednisolone. Living-donor kidney transplantation was performed because his anti-GBM antibody had remained undetectable for 1 year after diagnosis. In the main text, clinicopathological characteristics of 12 patients with anti-GBM disease at our institution were summarized. Conclusions We found that the 1-year survival rate of patients with anti-GBM disease was 88% in our cohort, which was comparable to previous studies. Multicenter, nationwide studies are expected to evaluate prognosis of Japanese patients with this rare entity.

Download Full-text