Use of genomic and functional analysis to characterize patients with steroid-resistant nephrotic syndrome.
Background: Children with genetic causes of steroid-resistant nephrotic syndrome (SRNS) usually do well after renal transplantation, while some with idiopathic SRNS show recurrence due to a putative podocyte-toxic factor. Distinguishing different forms of SRNS based on clinical criteria has been dif...
| Publicado en: | Pediatric Nephrology Vol. 33; no. 10; pp. 1741 - 1751 |
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| Autores principales: | , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Springer Nature
Oct2018
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=131661166&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 131661166 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 0931041X EF1 jtl: Pediatric Nephrology issn: 0931041X maglogo: N pubinfo: dt: Oct2018 vid: 33 iid: 10 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 131661166 131661166 131661166 10.1007/s00467-018-3995-2 131661166 ppf: 1741 ppct: 10 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Use of genomic and functional analysis to characterize patients with steroid-resistant nephrotic syndrome. aug: au: Kitzler, Thomas M. Kachurina, Nadezda Bitzan, Martin M. Torban, Elena Goodyer, Paul R. affil: Department of Medical Genetics, The Montreal Children’s Hospital, McGill University Health Center, Montreal, Quebec, Canada sug: subj: Nephrotic Syndrome Familial and Genetic Nephrotic Syndrome Diagnosis Steroids Drug Resistance Sequence Analysis Methods Biological Assay Human Epithelial Cells Analysis Mutation Recurrence Risk Factors Confidence Intervals Nephrotic Syndrome Blood Grafts Nephrotic Syndrome Surgery Postoperative Complications Kidney Transplantation Cell-Matrix Junctions ab: Background: Children with genetic causes of steroid-resistant nephrotic syndrome (SRNS) usually do well after renal transplantation, while some with idiopathic SRNS show recurrence due to a putative podocyte-toxic factor. Distinguishing different forms of SRNS based on clinical criteria has been difficult. The aim of our study was to test a novel approach that allows categorization of patients into clinically useful subgroups.Methods: Seventeen patients with clinically confirmed SRNS were analyzed by next-generation sequencing (NGS) of 37 known SRNS genes and a functional assay of cultured human podocytes, which indirectly tests for toxicity of patients’ sera by evidenced loss of podocyte focal adhesion complex (FAC) number.Results: We identified a pathogenic mutation in seven patients (41%). Sera from patients with monogenic SRNS caused mild loss of FAC number down to 73% compared to untreated controls, while sera from seven of the remaining ten patients with idiopathic SRNS caused significant FAC number loss to 43% (non-overlapping difference 30%, 95% CI 26-36%, P < 0.001). All patients with recurrent SRNS (n = 4) in the graft showed absence of podocyte gene mutations but significant FAC loss. Three patients had no mutation nor serum podocyte toxicity.Conclusions: Our approach allowed categorization of patients into three subgroups: (1) patients with monogenic SRNS; (2) patients with idiopathic SRNS and marked serum podocyte toxicity; and (3) patients without identifiable genetic cause nor evidence of serum podocyte toxicity. Post-transplant SRNS recurrence risk appears to be low in groups 1 and 3, but high in group 2. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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