Focal segmental glomerulosclerosis: molecular genetics and targeted therapies

Chen, Ying Maggie; Liapis, Helen

doi:10.1186/s12882-015-0090-9

Cited by 48 publications

(42 citation statements)

References 112 publications

(95 reference statements)

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“…Critical is the elimination of other systemic diseases or primary renal diseases that may result in a similar presentation. Many reviews cover various aspects of FSGS and include comprehensive reviews (1)(2)(3)(4), disease mechanisms (5)(6)(7)(8), pediatric disease (9), immunologic aspects (10), treatment in children (11), and treatment in adults (12)(13)(14). We focus here on a practical approach to FSGS assessment on clinical and histopathologic grounds in the context of our current understanding of disease mechanisms and genetics.…”

Section: Introductionmentioning

confidence: 99%

Focal Segmental Glomerulosclerosis

Rosenberg

Kopp

2017

CJASN

389

356

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Focal segmental glomerulosclerosis (FSGS) is a leading cause of kidney disease worldwide. The presumed etiology of primary FSGS is a plasma factor with responsiveness to immunosuppressive therapy and a risk of recurrence after kidney transplant-important disease characteristics. In contrast, adaptive FSGS is associated with excessive nephron workload due to increased body size, reduced nephron capacity, or single glomerular hyperfiltration associated with certain diseases. Additional etiologies arenow recognized asdrivers of FSGS: high-penetrance geneticFSGSdue to mutations in one of nearly 40 genes, virus-associated FSGS, and medication-associated FSGS. Emerging data support the identification of a sixth category: APOL1 risk allele-associated FSGS in individuals with sub-Saharan ancestry. The classification of a particular patient with FSGS relies on integration of findings from clinical history, laboratory testing, kidney biopsy, and in some patients, genetic testing. The kidney biopsy can be helpful, with clues provided by features on light microscopy (e.g., glomerular size, histologic variant of FSGS, microcystic tubular changes, and tubular hypertrophy), immunofluorescence (e.g., to rule out other primary glomerulopathies), and electron microscopy (e.g., extent of podocyte foot process effacement, podocyte microvillous transformation, and tubuloreticular inclusions). A complete assessment of renal histology is important for establishing the parenchymal setting of segmental glomerulosclerosis, distinguishing FSGS associated with one of many other glomerular diseases from the clinical-pathologic syndrome of FSGS. Genetic testing is beneficial in particular clinical settings. Identifying the etiology of FSGS guides selection of therapy and provides prognostic insight. Much progress has been made in our understanding of FSGS, but important outstanding issues remain, including the identity of the plasma factor believed to be responsible for primary FSGS, the value of routine implementation of genetic testing, and the identification of more effective and less toxic therapeutic interventions for FSGS.

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Section: Introductionmentioning

confidence: 99%

Focal Segmental Glomerulosclerosis

Rosenberg

Kopp

2017

CJASN

389

356

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“…Focal segmental glomerular sclerosis (FSGS) is a lesion of the kidney glomerulus that leads to nephrotic syndrome, typically progressing to end stage renal disease [Chen and Liapis, 2015; Jefferson and Shankland, 2014; Rood et al, 2012]. The key targets of this lesion are podocytes, highly specialized epithelial cells that enwrap the glomerular capillaries with highly elaborate foot processes [Jefferson and Shankland, 2014].…”

Section: The Role Of Inf2 In Human Diseasementioning

confidence: 99%

Inverted formins: A subfamily of atypical formins

2017

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Formins are a family of regulators of actin and microtubule dynamics that are present in almost all eukaryotes. These proteins are involved in many cellular processes, including cytokinesis, stress fiber formation, and cell polarization. Here we review one sub-family of formins, the inverted formins. Inverted formins as a group break several formin stereotypes, having atypical biochemical properties and domain organization, and they have been linked to kidney disease and neuropathy in humans. In this review, we will explore recent research on members of the inverted formin sub-family in mammals, zebrafish, fruit flies, and worms.

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“…Most of these genes can be categorized as those which are related with slit diaphragm structure, actin cytoskeleton of podocytes, or podocyte-glomerular basement membrane interaction through foot processes [37-39]. In addition, a specific channel mutation (see below) has also been identified as a cause of FSGS (Table 1).…”

Section: Genetic Backgroundmentioning

confidence: 99%

Pathogenesis of Focal Segmental Glomerulosclerosis

Lim

Yang

Sung

et al. 2016

J Pathol Transl Med

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Focal segmental glomerulosclerosis (FSGS) is characterized by focal and segmental obliteration of glomerular capillary tufts with increased matrix. FSGS is classified as collapsing, tip, cellular, perihilar and not otherwise specified variants according to the location and character of the sclerotic lesion. Primary or idiopathic FSGS is considered to be related to podocyte injury, and the pathogenesis of podocyte injury has been actively investigated. Several circulating factors affecting podocyte permeability barrier have been proposed, but not proven to cause FSGS. FSGS may also be caused by genetic alterations. These genes are mainly those regulating slit diaphragm structure, actin cytoskeleton of podocytes, and foot process structure. The mode of inheritance and age of onset are different according to the gene involved. Recently, the role of parietal epithelial cells (PECs) has been highlighted. Podocytes and PECs have common mesenchymal progenitors, therefore, PECs could be a source of podocyte repopulation after podocyte injury. Activated PECs migrate along adhesion to the glomerular tuft and may also contribute to the progression of sclerosis. Markers of activated PECs, including CD44, could be used to distinguish FSGS from minimal change disease. The pathogenesis of FSGS is very complex; however, understanding basic mechanisms of podocyte injury is important not only for basic research, but also for daily diagnostic pathology practice.

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Focal segmental glomerulosclerosis: molecular genetics and targeted therapies

Cited by 48 publications

References 112 publications

Focal Segmental Glomerulosclerosis

Focal Segmental Glomerulosclerosis

Inverted formins: A subfamily of atypical formins

Pathogenesis of Focal Segmental Glomerulosclerosis

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