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Circulating Permeability Factors in Idiopathic Nephrotic Syndrome and Focal Segmental Glomerulosclerosis

Ellen T. McCarthy, Mukut Sharma and Virginia J. Savin
CJASN November 2010, 5 (11) 2115-2121; DOI: https://doi.org/10.2215/CJN.03800609
Ellen T. McCarthy
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Mukut Sharma
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Virginia J. Savin
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Abstract

Circulating permeability factors may be important in idiopathic nephrotic syndrome (INS) including focal segmental glomerulosclerosis (FSGS) and in recurrence after renal transplantation. Evidence for plasma factors includes posttransplant recurrence of proteinuria and its response to plasmapheresis or immunoadsorption and induction of proteinuria in experimental animals by infusion of patient plasma or its fractions. The authors and other investigators have used proteomic techniques to seek pathogenic molecules. The authors have recently proposed cardiotrophin-like cytokine-1 (CLC-1) as an active factor in FSGS. Other potential permeability factors include hemopexin and vascular permeability factor in minimal change nephrotic syndrome (MCNS) and soluble urokinase receptor in FSGS. In the authors' studies, in vitro plasma permeability activity is blocked by diverse substances that may decrease levels of active molecules or block the effects of circulating permeability factors. It has been shown that the simple sugar galactose blocks the effect of FSGS serum on albumin permeability in vitro and decreases permeability activity when administered to patients. Because identities of permeability factors and their mechanisms of action are not well defined, therapy of INS/FSGS is empiric. Corticosteroids are the mainstay of initial therapy whereas calcineurin inhibitors such as cyclosporine A (CsA) and immunosuppressive medications provide adjunctive therapy. Nonspecific therapies such as blocking the renin-angiotensin system and controlling blood pressure and plasma lipids may also diminish proteinuria and slow progression. Identification of molecules that initiate proteinuria and application of findings from in vitro studies may lead to development of new treatments to arrest progression and prevent recurrence after transplantation.

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    • Copyright © 2010 by the American Society of Nephrology
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    Clinical Journal of the American Society of Nephrology
    Vol. 5, Issue 11
    1 Nov 2010
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    Circulating Permeability Factors in Idiopathic Nephrotic Syndrome and Focal Segmental Glomerulosclerosis
    Ellen T. McCarthy, Mukut Sharma, Virginia J. Savin
    CJASN Nov 2010, 5 (11) 2115-2121; DOI: 10.2215/CJN.03800609

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    Circulating Permeability Factors in Idiopathic Nephrotic Syndrome and Focal Segmental Glomerulosclerosis
    Ellen T. McCarthy, Mukut Sharma, Virginia J. Savin
    CJASN Nov 2010, 5 (11) 2115-2121; DOI: 10.2215/CJN.03800609
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    • Article
      • Abstract
      • Clinical Course and Therapy
      • Permeability Factors in MCNS
      • Permeability Factors in FSGS
      • Differentiation between MCNS and FSGS
      • Posttransplant Recurrence of NS/FSGS
      • Prevention of Recurrence
      • Permeability Factors in FSGS and Posttransplant Recurrence
      • Functional Properties of FSGS Permeability Factor and Clinical Associations
      • Observations with Implications for Future Therapy
      • Standard Therapy and Potential New Therapies
      • Summary
      • Disclosures
      • Acknowledgments
      • Footnotes
      • References
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    Cited By...

    • A Systematic Analysis of Major Susceptible Genes in Childhood-onset Steroid-resistant Nephrotic Syndrome
    • Clinical Significance of IgM and C3 Glomerular Deposition in Primary Focal Segmental Glomerulosclerosis
    • TLR-mediated albuminuria needs TNF{alpha}-mediated cooperativity between TLRs present in hematopoietic tissues and CD80 present on non-hematopoietic tissues in mice
    • Rethinking First-Line Immunosuppression for Idiopathic FSGS
    • Rituximab in Children with Steroid-Dependent Nephrotic Syndrome: A Multicenter, Open-Label, Noninferiority, Randomized Controlled Trial
    • Sphingomyelinase-Like Phosphodiesterase 3b Expression Levels Determine Podocyte Injury Phenotypes in Glomerular Disease
    • Relationship between Serum Soluble Urokinase Plasminogen Activator Receptor Level and Steroid Responsiveness in FSGS
    • De Novo Glomerular Diseases after Renal Transplantation
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    • Treatment of Primary FSGS in Adults
    • The Plasma Permeability Factor in Nephrotic Syndrome: Indirect Evidence in Pediatric Peritoneal Dialysis
    • Basic and Translational Concepts of Immune-Mediated Glomerular Diseases
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