Dataset Information

A circulating permeability factor in focal segmental glomerulosclerosis: the hunt continues.

ABSTRACT: Primary focal segmental glomerulosclerosis (FSGS) is one of the major causes of steroid-resistant nephrotic syndrome, and renal prognosis in patients with steroid-resistant FSGS is poor. It has been long speculated that a circulating permeability factor should be implicated in the pathogenesis of the disease because a substantial portion of the patients with primary FSGS experience recurrence shortly after transplantation. Although molecules such as cardiotrophin-like cytokine 1 (CLC-1) and anti-CD40 antibody have been proposed to be potential circulating permeability factors, a definitive factor remains to be discovered. Soluble urokinase-type plasminogen activator receptor (suPAR) has attracted substantial attention and garnered scrutiny by renal researchers since Reiser's group suggested that it was linked to the pathogenesis of primary FSGS and that it might be useful as a diagnostic biomarker. A number of different cohort studies have shown that serum suPAR levels are negatively associated with renal function and can scarcely differentiate FSGS from the other glomerular/renal diseases. In contrast to initial studies, several in vivo studies investigating the effects of forced suPAR upregulation could not show the induction of proteinuria or podocyte injury. Currently it is suggested that a different form of suPAR, which cannot be measured by presently available enzyme-linked immunosorbent assay, might be the culprit; however, it remains to be determined whether this is the case. Because a circulating permeability factor might be a useful biomarker for diagnosing FSGS as well as a potent therapeutic target for primary and recurrent FSGS, further dedicated work will be needed.

SUBMITTER: Wada T

PROVIDER: S-EPMC4655796 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A circulating permeability factor in focal segmental glomerulosclerosis: the hunt continues.

Wada Takehiko T Nangaku Masaomi M

Clinical kidney journal 20150915 6

Primary focal segmental glomerulosclerosis (FSGS) is one of the major causes of steroid-resistant nephrotic syndrome, and renal prognosis in patients with steroid-resistant FSGS is poor. It has been long speculated that a circulating permeability factor should be implicated in the pathogenesis of the disease because a substantial portion of the patients with primary FSGS experience recurrence shortly after transplantation. Although molecules such as cardiotrophin-like cytokine 1 (CLC-1) and anti ...[more]

PMID: 26613029

Similar Datasets

Project description: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 are now recognized as drivers of FSGS: high-penetrance genetic FSGS due 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.

Dataset Information

A circulating permeability factor in focal segmental glomerulosclerosis: the hunt continues.

Publications

A circulating permeability factor in focal segmental glomerulosclerosis: the hunt continues.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets