Clinical and pathological phenotype of genetic causes of focal segmental glomerulosclerosis in adults

Lepori, Nicola; Zand, Ladan; Sethi, Sanjeev; Fernández-Juárez, Gema; Fervenza, Fernando C.

doi:10.1093/ckj/sfx143

Cited by 68 publications

(72 citation statements)

References 75 publications

(102 reference statements)

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“…Many of these patients may have an undiagnosed genetic basis of FSGS. 68 New sequencing technologies have dramatically increased the sensitivity for disease-associated variants and mutations compared with the traditional Sanger sequencing. However, many of those genetic abnormalities require additional hits, such as other susceptibility genes or disease-related stressors, before FSGS ensues.…”

Section: Resultsmentioning

confidence: 99%

Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic Approach

Vriese

Sethi²,

Nath

et al. 2018

JASN

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FSGS describes a renal histologic lesion with diverse causes and pathogenicities that are linked by podocyte injury and depletion. Subclasses of FSGS include primary, genetic, and secondary forms, the latter comprising maladaptive, viral, and drug-induced FSGS. Despite sharing certain clinical and histologic features, these subclasses differ noticeably in management and prognosis. Without an accepted nongenetic biomarker that discriminates among these FSGS types, classification of patients is often challenging. This review summarizes the clinical and histologic features, including the onset and severity of proteinuria as well as the presence of nephrotic syndrome, that may aid in identifying the specific FSGS subtype. The FSGS lesion is characterized by segmental sclerosis and must be differentiated from nonspecific focal global glomerulosclerosis. No light microscopic features are pathognomonic for a particular FSGS subcategory. The characteristics of podocyte foot process effacement on electron microscopy, while helpful in discriminating between primary and maladaptive FSGS, may be of little utility in detecting genetic forms of FSGS. When FSGS cannot be classified by clinicopathologic assessment, genetic analysis should be offered. Next generation DNA sequencing enables cost-effective screening of multiple genes simultaneously, but determining the pathogenicity of a detected genetic variant may be challenging. A more systematic evaluation of patients, as suggested herein, will likely improve therapeutic outcomes and the design of future trials in FSGS.

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Section: Resultsmentioning

confidence: 99%

Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic Approach

Vriese

Sethi²,

Nath

et al. 2018

JASN

Self Cite

230

245

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“…En nuestro paciente, el patrón inespecífico de esclerosis (NOS), sin depósitos inmunes y con fusión pedicelar completa, es sugerente de una GSFS primaria 16 , no observándose glomerulomegalia o distribución preferentemente perihiliar de la lesión, propias de las formas adaptativas con hiperfiltración como se describe en la obesidad y post-nefrectomía 17 . Sin perjuicio de lo anterior y aunque no existen antecedentes familiares de nefropatía, debemos destacar que la presentación histológica de una GSFS primaria puede ser indistinguible de aquella producida por las mutaciones genéticas 18 , estudio que no fue realizado. Adicionalmente, algunas GSFS han sido asociadas al uso de fármacos (litio, sirolimus) o drogas (heroína), algunas de las cuales pueden inducir además hepatoxicidad (anabólicos) las que no son planteables en este caso 19 .…”

Section: Discussionunclassified

Daño hepatocelular, proteinuria y autoinmunidad: ¿enfermedad multisistémica o coincidencia de enfermedades? Caso clínico

et al. 2018

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We report a 19 years old male presenting with knee pain, elevated liver enzymes and proteinuria. Further investigation found positive antinuclear and anti-smooth muscle antibodies and a liver biopsy revealed the presence of an autoimmune hepatitis. Treatment with corticosteroids and azathioprine was started, resulting in normalization of liver enzymes but proteinuria persisted and a kidney biopsy disclosed a focal segmental glomerulosclerosis. The use of lisinopril resulted in a significative reduction of proteinuria and, after 30 months of follow up, he continues with azathioprine, lisinopril and a low prednisone dose without evidence of liver or kidney disease activity.

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“…Generally, their onset is usually in late youth or early adulthood, causes a slow progressive damage, and their clinical and pathological characteristics mimic those of secondary FSGS forms. Further environmental, genetic, or epigenetic modifiers could explain the development of distinct phenotypes in family members affected by the same mutation [27, 28]. In addition to mutations in genes encoding podocyte-specific proteins, mutations in other genes such as the COQ2 gene, Wilms’ tumor gene (WT1), and gene for LIM homeobox transcription factor 1β (LMX1B), which is a transcription factor required for the expression of CD2AP and NPHS2, associated with nail-patella syndrome, are associated with syndromes of which FSGS is often a part [4].…”

Section: Pathogenesismentioning

confidence: 99%

Focal Segmental Glomerulosclerosis: State-of-the-Art and Clinical Perspective

Shabaka

Ribera

Fernández-Juárez³

2020

Nephron

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Focal segmental glomerulosclerosis (FSGS) is a histological pattern of glomerular injury, rather than a single disease, that is caused by diverse clinicopathological entities with different mechanisms of injury with the podocyte as the principal target of lesion, leading to the characteristic sclerotic lesions in parts (i.e., focal) of some (i.e., segmental) glomeruli. The lesion of FSGS has shown an increasing prevalence over the past few decades and is considered the most common glomerular cause leading to ESKD. Primary FSGS, which usually presents with nephrotic syndrome, is thought to be caused by circulating permeability factors that have a main role in podocyte foot process effacement. Secondary forms of FSGS include maladaptive FSGS secondary to glomerular hyperfiltration such as in obesity or in cases of loss in nephron mass, virus-associated FSGS, and drugassociated FSGS that can result in direct podocyte injury. Genetic FSGS is increasingly been recognized and a careful evaluation of patients with atypical primary or secondary FSGS should be performed to exclude genetic causes. Unlike primary FSGS, secondary and genetic forms of FSGS do not respond to immunosuppression and tend not to recur after kidney transplantation. Distinguishing primary FSGS from secondary and genetic causes has a prognostic significance and is crucial for an appropriate management. In this review, we examine the pathogenesis, clinical approach to distinguish between the different causes, and current recommendations in the management of FSGS.

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Clinical and pathological phenotype of genetic causes of focal segmental glomerulosclerosis in adults

Cited by 68 publications

References 75 publications

Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic Approach

Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic Approach

Daño hepatocelular, proteinuria y autoinmunidad: ¿enfermedad multisistémica o coincidencia de enfermedades? Caso clínico

Focal Segmental Glomerulosclerosis: State-of-the-Art and Clinical Perspective

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