title: Lessons from genetics: is it time to revise the therapeutic approach to children with steroid-resistant nephrotic syndrome?
abstract: Primitive nephrotic syndrome is one of the most common glomerular diseases in childhood and represents the clinical manifestation of various pathologic changes in the kidney. In children, nephrotic syndrome is classified based on the initial response to empiric corticosteroid treatment, which is considered as the best predictor of patients' final outcome. The advent of next-generation sequencing technology showed that genetic alterations in structural genes of the podocyte can be recognized in a significant proportion of not only familial or syndromic patients with steroid-resistant nephrotic syndrome (SRNS), but also of sporadic cases, raising the question of whether it is time to update current protocols of patient care. In this review, we discuss the implications derived from several studies describing a high prevalence in children with SRNS of pathogenic mutations in a group of genes and their unresponsiveness to immunosuppressive therapy. We propose a diagnostic and therapeutic algorithm to reduce the exposure to immunosuppressants in individuals with unresponsive forms of the disease, sparing patients the untoward side effects of prolonged ineffective treatments, and at the same time guaranteeing the optimal immunosuppressive or other new therapy in potentially responsive patients.
authors.affiliation: Nephrology and Dialysis Unit, Meyer Children's Hospital, Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Becherucci
authors.affiliation: Nephrology and Dialysis Unit, Meyer Children's Hospital, Florence, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Mazzinghi
authors.affiliation: Medical Genetics Unit, Meyer Children's Hospital, Florence, Italy.
authors.forename: Aldesia
authors.initials: A
authors.lastname: Provenzano
authors.affiliation: Department of Pediatrics, University of Padua, Padua, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Murer
authors.affiliation: Medical Genetics Unit, Meyer Children's Hospital, Florence, Italy.|Department of Biomedical Experimental and Clinical Sciences "Mario Serio", University of Florence, Viale Pieraccini 6, 50139, Florence, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Giglio
authors.affiliation: Nephrology and Dialysis Unit, Meyer Children's Hospital, Florence, Italy. p.romagnani@dfc.unifi.it.|Department of Biomedical Experimental and Clinical Sciences "Mario Serio", University of Florence, Viale Pieraccini 6, 50139, Florence, Italy. p.romagnani@dfc.unifi.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Romagnani
mesh_terms: D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance / Q000235:genetics*; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D009404:Nephrotic Syndrome / Q000151:congenital* / Q000188:drug therapy / Q000235:genetics
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents
keywords: Children; Gene; Genetics; Immunosuppressive therapy; Mutation; Steroid-resistant nephrotic syndrome