PT  - JOURNAL ARTICLE
AU  - Trautmann, Agnes
AU  - Bodria, Monica
AU  - Ozaltin, Fatih
AU  - Gheisari, Alaleh
AU  - Melk, Anette
AU  - Azocar, Marta
AU  - Anarat, Ali
AU  - Caliskan, Salim
AU  - Emma, Francesco
AU  - Gellermann, Jutta
AU  - Oh, Jun
AU  - Baskin, Esra
AU  - Ksiazek, Joanna
AU  - Remuzzi, Giuseppe
AU  - Erdogan, Ozlem
AU  - Akman, Sema
AU  - Dusek, Jiri
AU  - Davitaia, Tinatin
AU  - Özkaya, Ozan
AU  - Papachristou, Fotios
AU  - Firszt-Adamczyk, Agnieszka
AU  - Urasinski, Tomasz
AU  - Testa, Sara
AU  - Krmar, Rafael T.
AU  - Hyla-Klekot, Lidia
AU  - Pasini, Andrea
AU  - Özcakar, Z. Birsin
AU  - Sallay, Peter
AU  - Cakar, Nilgun
AU  - Galanti, Monica
AU  - Terzic, Joelle
AU  - Aoun, Bilal
AU  - Caldas Afonso, Alberto
AU  - Szymanik-Grzelak, Hanna
AU  - Lipska, Beata S.
AU  - Schnaidt, Sven
AU  - Schaefer, Franz
TI  - Spectrum of Steroid-Resistant and Congenital Nephrotic Syndrome in Children: The PodoNet Registry Cohort
AID  - 10.2215/CJN.06260614
DP  - 2015 Apr 07
TA  - Clinical Journal of the American Society of Nephrology
PG  - 592--600
VI  - 10
IP  - 4
4099  - http://cjasn.asnjournals.org/content/10/4/592.short
4100  - http://cjasn.asnjournals.org/content/10/4/592.full
SO  - CLIN J AM SOC NEPHROL2015 Apr 07; 10
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.