RT Journal Article
SR Electronic
T1 Spectrum of Steroid-Resistant and Congenital Nephrotic Syndrome in Children: The PodoNet Registry Cohort
JF Clinical Journal of the American Society of Nephrology
JO CLIN J AM SOC NEPHROL
FD American Society of Nephrology
SP 592
OP 600
DO 10.2215/CJN.06260614
VO 10
IS 4
A1 Trautmann, Agnes
A1 Bodria, Monica
A1 Ozaltin, Fatih
A1 Gheisari, Alaleh
A1 Melk, Anette
A1 Azocar, Marta
A1 Anarat, Ali
A1 Caliskan, Salim
A1 Emma, Francesco
A1 Gellermann, Jutta
A1 Oh, Jun
A1 Baskin, Esra
A1 Ksiazek, Joanna
A1 Remuzzi, Giuseppe
A1 Erdogan, Ozlem
A1 Akman, Sema
A1 Dusek, Jiri
A1 Davitaia, Tinatin
A1 Özkaya, Ozan
A1 Papachristou, Fotios
A1 Firszt-Adamczyk, Agnieszka
A1 Urasinski, Tomasz
A1 Testa, Sara
A1 Krmar, Rafael T.
A1 Hyla-Klekot, Lidia
A1 Pasini, Andrea
A1 Özcakar, Z. Birsin
A1 Sallay, Peter
A1 Cakar, Nilgun
A1 Galanti, Monica
A1 Terzic, Joelle
A1 Aoun, Bilal
A1 Caldas Afonso, Alberto
A1 Szymanik-Grzelak, Hanna
A1 Lipska, Beata S.
A1 Schnaidt, Sven
A1 Schaefer, Franz
YR 2015
UL http://cjasn.asnjournals.org/content/10/4/592.abstract
AB 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.