Use of genomic and functional analysis to characterize patients with steroid-resistant nephrotic syndrome.
Pediatr Nephrol
; 33(10): 1741-1750, 2018 10.
Article
en En
| MEDLINE
| ID: mdl-29982877
ABSTRACT
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Resistencia a Medicamentos
/
Podocitos
/
Glucocorticoides
/
Síndrome Nefrótico
Tipo de estudio:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adolescent
/
Adult
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Pediatr Nephrol
Asunto de la revista:
NEFROLOGIA
/
PEDIATRIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Canadá