An Overlapping Case of Alport Syndrome and Thin Basement Membrane Disease

Initially, the thin glomerular basement membrane disease was called “a gentle and curable hemorrhagic nephritis”. The thin basement membrane disease has been finally characterized at the beginning of 1970s. This is when the connection between previously clinically described gentle microhematuria and significant thinning of glomerular basement membrane discovered during examination under the electron-microscope has been established. Ultimately, the disease has been described as a condition characterized with a diverse clinical course, usually mild, but sometimes progressive. It is a family conditioned disease, but it also appears sporadically and concerns at least 1% of the population. It has also been stated that it is one of the most frequent renal diseases, enumerated directly after changes caused by infections, hypertension and renal lithiasis. This particular disease is diagnosed more often than IgA nephropathy and Alport syndrome, which are also associated with haematuria or microhematuria.

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Prevalence of clinical, pathological and molecular features of glomerular basement membrane nephropathy caused by COL4A3 or COL4A4 mutations: a systematic review

Clinical Kidney Journal ◽

10.1093/ckj/sfz176 ◽

2020 ◽

Vol 13 (6) ◽

pp. 1025-1036 ◽

Cited By ~ 3

Author(s):

Andreas Matthaiou ◽

Tsielestina Poulli ◽

Constantinos Deltas

Keyword(s):

Basement Membrane ◽

Alport Syndrome ◽

Autosomal Dominant ◽

Wide Spectrum ◽

Age At Onset ◽

Histological Finding ◽

Basement Membranes ◽

Thin Basement Membrane Nephropathy ◽

Molecular Features ◽

Thin Basement Membrane Disease

Abstract Background Patients heterozygous for COL4A3 or COL4A4 mutations show a wide spectrum of disease, extending from familial isolated microscopic haematuria, as a result of thin basement membranes (TBMs), to autosomal dominant Alport syndrome (ADAS) and end-stage renal disease (ESRD). Many patients are mentioned in the literature under the descriptive diagnosis of TBM nephropathy (TBMN), in which case it actually describes a histological finding that represents the carriers of autosomal recessive Alport syndrome (ARAS), a severe glomerulopathy, as most patients reach ESRD at a mean age of 25 years. Methods We performed a systematic literature review for patients with heterozygous COL4A3/A4 mutations with the aim of recording the spectrum and frequency of pathological features. We searched three databases (PubMed, Embase and Scopus) using the keywords ‘Autosomal Dominant Alport Syndrome’ OR ‘Thin Basement Membrane Disease’ OR ‘Thin Basement Membrane Nephropathy’. We identified 48 publications reporting on 777 patients from 258 families. Results In total, 29% of the patients developed chronic kidney disease (CKD) and 15.1% reached ESRD at a mean age of 52.8 years. Extrarenal features and typical Alport syndrome (AS) findings had a low prevalence in patients as follows: hearing loss, 16%; ocular lesions, 3%; basement membrane thickening, 18.4%; and podocyte foot process effacement, 6.9%. Data for 76 patients from 54 families emphasize extensive inter- and intrafamilial heterogeneity, with age at onset of ESRD ranging between 21 and 84 years (mean 52.8). Conclusions The analysis enabled a comparison of the clinical course of patients with typical ARAS or X-linked AS with those with heterozygous COL4A mutations diagnosed with TBMN or ADAS. Despite the consequence of a potential ascertainment bias, an important outcome is that TBM poses a global high risk of developing severe CKD, over a long follow-up, with a variable spectrum of other findings. The results are useful to practicing nephrologists for better evaluation of patients.

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Alport syndrome and benign familial hematuria (thin basement membrane disease) in two brothers of a family with hematuria

Clinical Nephrology ◽

10.5414/cnp60195 ◽

2003 ◽

Vol 60 (09) ◽

pp. 195-200 ◽

Cited By ~ 5

Author(s):

T. Takemura ◽

H. Yanagida ◽

K. Yagi ◽

K. Moriwaki ◽

M. Okada

Keyword(s):

Basement Membrane ◽

Alport Syndrome ◽

Thin Basement Membrane Disease ◽

Benign Familial Hematuria ◽

Familial Hematuria

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Alport syndrome and thin basement membrane disease

Current Diagnostic Pathology ◽

10.1054/cdip.2002.0136 ◽

2002 ◽

Vol 8 (5) ◽

pp. 349-360 ◽

Cited By ~ 4

Author(s):

Clifford E. Kashtan

Keyword(s):

Basement Membrane ◽

Alport Syndrome ◽

Thin Basement Membrane Disease

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Difficulties in differentiating thin basement membrane disease from Alport syndrome

Polish Journal of Pathology ◽

10.5114/pjp.2016.65869 ◽

2016 ◽

Vol 4 ◽

pp. 357-363 ◽

Cited By ~ 1

Author(s):

Jakub Żurawski ◽

Paweł Burchardt ◽

Monika Seget ◽

Jerzy Moczko ◽

Aldona Woźniak ◽

...

Keyword(s):

Basement Membrane ◽

Alport Syndrome ◽

Thin Basement Membrane Disease

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A Model of Strain-Dependent Glomerular Basement Membrane Maintenance and Its Potential Ramifications in Health and Disease

Journal of Biomechanical Engineering ◽

10.1115/1.4007098 ◽

2012 ◽

Vol 134 (8) ◽

Cited By ~ 5

Author(s):

Victor H. Barocas ◽

Kevin D. Dorfman ◽

Yoav Segal

Keyword(s):

Pressure Drop ◽

Basement Membrane ◽

Glomerular Basement Membrane ◽

Alport Syndrome ◽

Published Data ◽

Model Parameters ◽

Structural Element ◽

Tissue Strain ◽

Thin Basement Membrane Disease ◽

Gbm Thickening

A model is developed and analyzed for type IV collagen turnover in the kidney glomerular basement membrane (GBM), which is the primary structural element in the glomerular capillary wall. The model incorporates strain dependence in both deposition and removal of the GBM, leading to an equilibrium tissue strain at which deposition and removal are balanced. The GBM thickening decreases tissue strain per unit of transcapillary pressure drop according to the law of Laplace, but increases the transcapillary pressure drop required to maintain glomerular filtration. The model results are in agreement with the observed GBM alterations in Alport syndrome and thin basement membrane disease, and the model-predicted linear relation between the inverse capillary radius and inverse capillary thickness at equilibrium is consistent with published data on different mammals. In addition, the model predicts a minimum achievable strain in the GBM based on the geometry, properties, and mechanical environment; that is, an infinitely thick GBM would still experience a finite strain. Although the model assumptions would be invalid for an extremely thick GBM, the minimum achievable strain could be significant in diseases, such as Alport syndrome, characterized by focal GBM thickening. Finally, an examination of reasonable values for the model parameters suggests that the oncotic pressure drop—the osmotic pressure difference between the plasma and the filtrate due to large molecules—plays an important role in setting the GBM strain and, thus, leakage of protein into the urine may be protective against some GBM damage.

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Segregation of hematuria in thin basement membrane disease with haplotypes at the loci for Alport syndrome

Kidney International ◽

10.1046/j.1523-1755.2001.0590051670.x ◽

2001 ◽

Vol 59 (5) ◽

pp. 1670-1676 ◽

Cited By ~ 52

Author(s):

Mark Buzza ◽

Diane Wilson ◽

Judy Savige

Keyword(s):

Basement Membrane ◽

Alport Syndrome ◽

Thin Basement Membrane Disease

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How genomics reclassifies diseases: the case of Alport syndrome

Clinical Kidney Journal ◽

10.1093/ckj/sfaa170 ◽

2020 ◽

Vol 13 (6) ◽

pp. 933-935 ◽

Cited By ~ 1

Author(s):

Roser Torra ◽

Monica Furlano ◽

Elisabet Ars

Keyword(s):

Basement Membrane ◽

Alport Syndrome ◽

Autosomal Dominant ◽

Wide Spectrum ◽

Unknown Origin ◽

Thin Basement Membrane Nephropathy ◽

Pathogenic Variants ◽

Thin Basement Membrane Disease ◽

Extreme Phenotypes ◽

Generation Sequencing

Abstract In this issue, Matthews et al. provide a comprehensive review of published cohorts with heterozygous pathogenic variants in COL4A3 or COL4A4, documenting the wide spectrum of the disease. Due to the extreme phenotypes that patients with heterozygous pathogenic variants in COL4A3 or COL4A4 may show, the disease has been referred to in a variety of ways, including ‘autosomal dominant Alport syndrome’, ‘thin basement membrane disease’, ‘thin basement membrane nephropathy’, ‘familial benign hematuria’ and ‘carriers of autosomal dominant Alport syndrome’. This confusion over terminology has prevented nephrologists from being sufficiently aware of the relevance of the entity. Nowadays, however, next-generation sequencing facilitates the diagnosis and it is becoming a relatively frequent finding in haematuric–proteinuric nephropathies of unknown origin, even in non-familial cases. There is a need to raise awareness among nephrologists about the disease in order to improve diagnosis and provide better management for these patients.

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Clinicopathologic and ultrastructural findings of hereditary nephritis; a 16-year single center survey in Iran

Journal of Renal Injury Prevention ◽

10.34172/jrip.2020.17 ◽

2020 ◽

Vol 9 (2) ◽

pp. e17-e17

Author(s):

Seyed Mohammad Owji ◽

Hadi Raeisi Shahraki ◽

Naser Pajouhi ◽

Seyed Hossein Owji ◽

Farshad Dehghani

Keyword(s):

Electron Microscopy ◽

Basement Membrane ◽

Light Microscopy ◽

Fabry Disease ◽

Toluidine Blue ◽

Alport Syndrome ◽

Blue Staining ◽

Toluidine Blue Staining ◽

Hereditary Nephritis ◽

Thin Basement Membrane Disease

Introduction: Hereditary nephritis is an umbrella term for a group of congenital childhood diseases including but not limited to Alport syndrome, thin basement membrane disease, and Fabry disease. Objectives: The purpose of this study was a clinicopathologic investigation of Alport syndrome, thin basement membrane disease, and Fabry disease with a focus on the role of electron microscopy and toluidine blue staining in diagnosis. Patients and Methods: In this cross-sectional study, we investigated kidney biopsies with a final diagnosis of either Alport syndrome, thin basement membrane disease or Fabry disease from 2001 to 2016. Electron microscopy and light microscopy were done and the clinical and paraclinical data were extracted from the patients’ medical charts. Electron microscopy role was assessed in terms of necessary, helpful or non-necessary, while correlations between clinical and para-clinical data were determined using appropriate statistical tests. Results: Among the 2865 kidney biopsies, there were 22 patients of hereditary nephritis including 15 (0.52%) Alport syndrome, 5 (0.17%) thin basement membrane disease and 2 (0.07%) Fabry disease diagnosed by electron microscopy. Electron microscopy was essential for the diagnosis of 19 (86.4%) cases, helpful for 3(13.6%) and there was no case for which electron microscopy was non-necessary. The patients’ mean age was 16.1 ± 9.0 years. The most common finding in Alport syndrome was proteinuria (86.7%) followed by hematuria (60.0%). Conclusion: Considering the rate of misdiagnosis of hereditary nephritis using light microscopy and clinical findings alone, electron microscopy study and toluidine blue staining has an essential role in the precise diagnosis in these patients. With regard to the progressive nature of these diseases, prompt diagnosis using electron microscopy is pertinent for therapeutic decisions.

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