Pathologic glomerular characteristics and glomerular basement membrane alterations in biopsy-proven thin basement membrane nephropathy

Terasaki, Yasuhiro; Endo, Yoko; Terasaki, Mika; Κunugi, Shinobu; Igarashi, Toru; Mii, Akiko; Terasaki, Yasuhiro; Shimizu, Akira

doi:10.1007/s10157-018-01687-1

Cited by 8 publications

(8 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Typically, TBMN manifests as persistent microscopic haematuria in childhood; however, it is no longer considered benign as it is associated with progression to proteinuria and impaired kidney function in adults, with up to a 30% lifetime risk of kidney failure. Unlike XLAS in males and autosomal recessive AS, the 345 network is present in the mature GBM in TBMN but the GBM is diffusely thinned and use of LV-SEM has demonstrated the existence of irregular holes along the GBM surface 61 . The GBM thinning is likely explained by a gene dosage effect whereby podocytes that carry one abnormal copy of COL4A3, COL4A4 or COL4A5 produce fewer 345 trimers than podocytes that carry normal copies of both genes 134 .…”

Section: [H1] the Gbm In Glomerular Filtrationmentioning

confidence: 95%

“…For instance, use of SBF-SEM demonstrated invasion of podocyte foot processes into damaged areas of GBM in various mouse models of glomerular disease 9 . Low-vacuum SEM [G] (LV-SEM), has been used to show the presence of spikes on the GBM and subepithelial electron-dense deposits in biopsy samples from patients with membranous nephropathy 59 , irregular GBM thickening and a basket-weave appearance in samples from patients with Alport syndrome 60 , and GBM thinning and perforation in samples from patients with thin basement membrane nephropathy (TBMN) 60,61 . Another emerging SEM technique called helium ion microscopy [G] (HIM) 62 has been used to reveal striking alterations on the surface of glomeruli from Col4a3 -/mice, including the deposition of long microfilaments, cytoplasmic bleb-like projections, and increased numbers of prominent podocyte bridge-like processes 63 .…”

Section: [H2] New Insights Into Gbm Compositionmentioning

confidence: 99%

See 1 more Smart Citation

Complexities of the glomerular basement membrane

2020

View full text Add to dashboard Cite

The glomerular basement membrane (GBM) is a key component of the glomerular capillary wall and is essential for kidney filtration. Major components of the GBM include laminins, collagen IV, nidogens and heparan sulphate proteoglycans. In addition, the GBM harbours a number of other structural and regulatory components and provides a reservoir for growth factors. New technologies have improved our ability to study the composition and assembly of basement membranes. We now know that the GBM is a complex macromolecular structure that undergoes key transitions during glomerular development. Defects in GBM components are associated with a range of hereditary human diseases such as Alport syndrome, which is caused by defects in the genes COL4A3, COL4A4 and COL4A5 and Pierson syndrome, which is caused by variants in LAMB2. In addition, the GBM is affected by acquired autoimmune disorders and metabolic disease such as diabetes mellitus. Current treatment for diseases associated with GBM involvement aims to reduce intraglomerular pressure and to treat the underlying cause where possible. As our understanding about the maintenance and turnover of the GBM improves, therapies to replace GBM components or to stimulate GBM repair could translate into new therapies for patients with GBM-associated disease.

show abstract

Section: [H1] the Gbm In Glomerular Filtrationmentioning

confidence: 95%

Section: [H2] New Insights Into Gbm Compositionmentioning

confidence: 99%

Complexities of the glomerular basement membrane

2020

View full text Add to dashboard Cite

show abstract

“…Three of the thin basement membrane disease cases were initially misdiagnosed as Alport syndrome. Of our five cases of thin basement membrane disease, three showed proteinuria and hematuria compared with a study in which 27 cases of thin basement membrane disease all had hematuria and 21 patients (77,8%) had proteinuria (20). A study by Mandache et al included 427 adult patients' kidney biopsy (36 being thin basement membrane disease and 10 Alport syndrome) and demonstrated the coexistence of glomerular diseases and thin basement membrane disease (the type with a mutation in type IV collagen genes, namely col4a3 and col4a3).…”

Section: Discussionmentioning

confidence: 64%

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

et al. 2020

View full text Add to dashboard Cite

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.

show abstract

“…In TBM, the expression of the GBM COLIV α5 chain is decreased, despite normal expression of COLIV α3 and COLIV α4. The role of the COLIV α5 chain in TBM pathogenesis is unknown [1,14,15]. The combined use of electron microscopy and immune-histochemical evaluation increases both sensitivity and specificity to TBM and Alport's diagnosis; however, the characteristic glomerular alterations Color version available online are not correlated with the degree of hematuria, proteinuria, or CKD [1,13].…”

Section: Introductionmentioning

confidence: 99%

“…The role of the COLIV α5 chain in TBM pathogenesis is unknown [1,14,15]. The combined use of electron microscopy and immune-histochemical evaluation increases both sensitivity and specificity to TBM and Alport's diagnosis; however, the characteristic glomerular alterations Color version available online are not correlated with the degree of hematuria, proteinuria, or CKD [1,13]. Healthy children and some patients with minimal-change nephropathy or other glomerulonephritis may also show thin GBM, but it is usually focal and not uniform as in TBM.…”

Section: Introductionmentioning

confidence: 99%

Thin Basement Membrane: An Underrated Cause of End-Stage Renal Disease

Uzzo

Moroni

Ponticelli³

2023

Nephron

View full text Add to dashboard Cite

The term “thin basement membrane” (TBM) refers to a glomerular disorder characterized by diffuse uniform thinning of the glomerular basement membrane (GBM) on electron microscopy. Patients with TBM usually show an isolated hematuria with excellent renal prognosis. However, some patients can develop proteinuria and progressive kidney dysfunction in the long term. Most patients with TBM are heterozygous for pathogenic variants in genes encoding for both the α3 and α4 chains of collagen IV, a major constituent of GBM. Such variants are responsible for a wide range of clinical and histological phenotypes. The differential diagnosis between TBM and autosomal-dominant Alport syndrome and IgA nephritis (IGAN) may be difficult in some cases. Patients who progress to chronic kidney disease may show clinicopathologic features similar to those of primary focal and segmental glomerular sclerosis (FSGS). Without a shared classification of these patients, the risk of misdiagnosis and/or underestimation of the risk of progressive kidney disease is real. New efforts are needed to understand the determinants of renal prognosis and recognize the early signs of renal deterioration, allowing a custom-made diagnosis and therapeutic approach. For this purpose, a practical and simple clinical approach is supplied.

show abstract

Pathologic glomerular characteristics and glomerular basement membrane alterations in biopsy-proven thin basement membrane nephropathy

Cited by 8 publications

References 24 publications

Complexities of the glomerular basement membrane

Complexities of the glomerular basement membrane

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

Thin Basement Membrane: An Underrated Cause of End-Stage Renal Disease

Contact Info

Product

Resources

About