Spectrum of steroid-resistant and congenital nephrotic syndrome in children: the PodoNet registry cohort.
Clin J Am Soc Nephrol
; 10(4): 592-600, 2015 Apr 07.
Article
en En
| MEDLINE
| ID: mdl-25635037
ABSTRACT
BACKGROUND AND OBJECTIVES:
Steroid-resistant nephrotic syndrome is a rare kidney disease involving either immune-mediated or genetic alterations of podocyte structure and function. The rare nature, heterogeneity, and slow evolution of the disorder are major obstacles to systematic genotype-phenotype, intervention, and outcome studies, hampering the development of evidence-based diagnostic and therapeutic concepts. To overcome these limitations, the PodoNet Consortium has created an international registry for congenital nephrotic syndrome and childhood-onset steroid-resistant nephrotic syndrome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Since August of 2009, clinical, biochemical, genetic, and histopathologic information was collected both retrospectively and prospectively from 1655 patients with childhood-onset steroid-resistant nephrotic syndrome, congenital nephrotic syndrome, or persistent subnephrotic proteinuria of likely genetic origin at 67 centers in 21 countries through an online portal.RESULTS:
Steroid-resistant nephrotic syndrome manifested in the first 5 years of life in 64% of the patients. Congenital nephrotic syndrome accounted for 6% of all patients. Extrarenal abnormalities were reported in 17% of patients. The most common histopathologic diagnoses were FSGS (56%), minimal change nephropathy (21%), and mesangioproliferative GN (12%). Mutation screening was performed in 1174 patients, and a genetic disease cause was identified in 23.6% of the screened patients. Among 14 genes with reported mutations, abnormalities in NPHS2 (n=138), WT1 (n=48), and NPHS1 (n=41) were most commonly identified. The proportion of patients with a genetic disease cause decreased with increasing manifestation age from 66% in congenital nephrotic syndrome to 15%-16% in schoolchildren and adolescents. Among various intensified immunosuppressive therapy protocols, calcineurin inhibitors and rituximab yielded consistently high response rates, with 40%-45% of patients achieving complete remission. Confirmation of a genetic diagnosis but not the histopathologic disease type was strongly predictive of intensified immunosuppressive therapy responsiveness. Post-transplant disease recurrence was noted in 25.8% of patients without compared with 4.5% (n=4) of patients with a genetic diagnosis.CONCLUSIONS:
The PodoNet cohort may serve as a source of reference for future clinical and genetic research in this rare but significant kidney disease.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Glomeruloesclerosis Focal y Segmentaria
/
Glomerulonefritis Membranoproliferativa
/
Nefrosis Lipoidea
/
Síndrome Nefrótico
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
/
Guideline
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
País/Región como asunto:
Asia
/
Europa
Idioma:
En
Revista:
Clin J Am Soc Nephrol
Asunto de la revista:
NEFROLOGIA
Año:
2015
Tipo del documento:
Article