Diagnostic and Prognostic Value of Miss-1 Study in Children and Adult With Nephrotic Syndrome MISSNEPHROTIQUE

Overview

The nephrotic syndrome is a rare disease defined by a proteinuria >3g/24h and a hypoalbuminemia < 30g/L. Genetic and immune are the main causes. The acquired idiopathic nephrotic syndrome presents histologically minimal glomerular lesions, sometimes associated with segmental and focal hyalinosis. The idiopathic nephrotic syndrome (INS) represents 85% of children's glomerular nephropathy and 25-30% of adult's. Relapses are frequents, and can be pejorative up to 10% and lead to end-stage kidney failure. Another immune cause is the extramembranous glomerulonephritis mediated by molecular targets specific autoantibodies expressed at the podocytes surface. Other immune causes include lupus nephropathy, ANCA vascularitis, Goodpasture disease, Berger disease. Easy diagnosis between these causes can be made with the renal biopsy. Miss-1, a new protein activated during a inflammatory event, could be an actor in nephrotic syndromes by modifying the podocyte's adhesion on the glomerular basal membrane. This would modulate the structure and function of the slit diaphragm, as well as junctions between the podocyte and the glomerular basal membrane, regulating podocytes' apoptosis.

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: October 2018

Detailed Description

This project is meant to propose and validate specific and non-invasive diagnostic and prognostic tests for the acquired idiopathic nephrotic syndrome. These tests rely on the measure of Miss-1 expression in circulating blood cells on flow cytometry and its plasmatic concentration. To date, no equivalent tests exist to diagnose idiopathic nephrotic syndrome (INS) from other causes. These simple tests would allow a quick diagnosis of acquired INS by avoiding an invasive renal biopsy. It would also help anticipate the relapses of the disease and guide the treatment modalities as do nowadays the PLA2R antibodies in idiopathic membranous nephropathy. We will propose the tests to every consent patient, hospitalized in the participating centers (Néphrologie pédiatrique of Robert Debré hospital, Néphrologie adulte of Tenon hospital) with a nephrotic syndrome.

Clinical Trial Outcome Measures

Primary Measures

  • Miss1 expression in circulating blood cells on flow cytometry at the time of diagnostic of nephrotic syndrome.
    • Time Frame: From Day 0 to 1 month
    • Sensitivity of the Miss1 test: The diagnosis will be made if the expression of Miss1 of circulating leukocytes in flow cytometry at the time of the diagnosis of nephrotic syndrome is> 20 times the mean value of the healthy controls.

Secondary Measures

  • Miss1 plasmatic concentration at the time of the diagnostic of nephrotic syndrome
    • Time Frame: From Day 0 to 1 month
    • Sensitivity of plasma Miss1 concentration for INS diagnosis. Specificity, PPV, NPV of the test in the child. Sensitivity, specificity, PPV, NPV of the diagnostic test of the monocyte and granulocyte membrane expression, of lymphocyte subpopulations, Treg and Th17, of the Miss-1 in flow cytometry at the time of the diagnosis of nephrotic syndrome> at a threshold.
  • Miss1 expression in circulating blood cells on flow cytometry after remission
    • Time Frame: After remission, up to 1 month
  • Miss1 plasmatic concentration after remission
    • Time Frame: After remission, up to 1 month

Participating in This Clinical Trial

Inclusion Criteria

  • All new hospitalized patient – Presenting a nephrotic syndrome according to its definition – For which an anatomopathological diagnostic and its evolution can be or will be carried – Children of any age can be included if they present a nephrotic syndrome Exclusion Criteria:

  • Patients already treated with glucocorticoids and/or immunosuppressor

Gender Eligibility: All

Minimum Age: 12 Months

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Assistance Publique – Hôpitaux de Paris
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Jean-Jacques Boffa, Professor, Principal Investigator, Assistance Publique – Hôpitaux de Paris
  • Overall Contact(s)
    • Jean-Jacques Boffa, Professor, 00 33 1 56 01 60 29, jean-jacques.boffa@aphp.fr

References

Shalhoub RJ. Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet. 1974 Sep 7;2(7880):556-60.

Eddy AA, Symons JM. Nephrotic syndrome in childhood. Lancet. 2003 Aug 23;362(9384):629-39. Review.

van den Berg JG, Weening JJ. Role of the immune system in the pathogenesis of idiopathic nephrotic syndrome. Clin Sci (Lond). 2004 Aug;107(2):125-36. Review.

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