BACKGROUND AND OBJECTIVES: Mutations in podocyte genes are associated with steroid-resistant nephrotic syndrome (SRNS), mostly affecting younger age groups. To date, it is unclear whether these patients benefit from intensified immunosuppression with cyclosporine A (CsA). The aim of this study was to evaluate the influence of podocyte gene defects in congenital nephrotic syndrome (CNS) and pediatric SRNS on the efficacy of CsA therapy and preservation of renal function. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: Genotyping was performed in 91 CNS/SRNS patients, irrespective of age at manifestation or response to CsA. RESULTS: Mutations were identified in 52% of families (11 NPHS1, 17 NPHS2, 11 WT1, 1 LAMB2, 3 TRPC6). Sixty-eight percent of patients with nongenetic SRNS responded to CsA, most of them achieved complete remission. In contrast, none of the patients with genetic CNS/SRNS experienced a complete remission and only two (17%) achieved a partial response, both affected by a WT1 mutation. Preservation of renal function was significantly better in children with nongenetic disease after a mean follow-up time of 8.6 years (ESRD in 29% versus 71%). CONCLUSIONS: The mutation detection rate in our population was high (52%). Most patients with genetic CNS/SRNS did not benefit from CsA with significantly lower response rates compared with nongenetic patients and showed rapid progression to end-stage renal failure. These data strongly support the idea not to expose CNS/SRNS patients with inherited defects related to podocyte function to intensified immunosuppression with CsA.
BACKGROUND AND OBJECTIVES: Mutations in podocyte genes are associated with steroid-resistant nephrotic syndrome (SRNS), mostly affecting younger age groups. To date, it is unclear whether these patients benefit from intensified immunosuppression with cyclosporine A (CsA). The aim of this study was to evaluate the influence of podocyte gene defects in congenital nephrotic syndrome (CNS) and pediatric SRNS on the efficacy of CsA therapy and preservation of renal function. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: Genotyping was performed in 91 CNS/SRNS patients, irrespective of age at manifestation or response to CsA. RESULTS: Mutations were identified in 52% of families (11 NPHS1, 17 NPHS2, 11 WT1, 1 LAMB2, 3 TRPC6). Sixty-eight percent of patients with nongenetic SRNS responded to CsA, most of them achieved complete remission. In contrast, none of the patients with genetic CNS/SRNS experienced a complete remission and only two (17%) achieved a partial response, both affected by a WT1 mutation. Preservation of renal function was significantly better in children with nongenetic disease after a mean follow-up time of 8.6 years (ESRD in 29% versus 71%). CONCLUSIONS: The mutation detection rate in our population was high (52%). Most patients with genetic CNS/SRNS did not benefit from CsA with significantly lower response rates compared with nongenetic patients and showed rapid progression to end-stage renal failure. These data strongly support the idea not to expose CNS/SRNS patients with inherited defects related to podocyte function to intensified immunosuppression with CsA.
Authors: A Philippe; S Weber; E L Esquivel; C Houbron; G Hamard; J Ratelade; W Kriz; F Schaefer; M-C Gubler; C Antignac Journal: Kidney Int Date: 2008-02-20 Impact factor: 10.612
Authors: Louise M McKenzie; Sher L Hendrickson; William A Briggs; Richard A Dart; Stephen M Korbet; Michelle H Mokrzycki; Paul L Kimmel; Tejinder S Ahuja; Jeffrey S Berns; Eric E Simon; Michael C Smith; Howard Trachtman; Donna M Michel; Jeffrey R Schelling; Monique Cho; Yu C Zhou; Elizabeth Binns-Roemer; Gregory D Kirk; Jeffrey B Kopp; Cheryl A Winkler Journal: J Am Soc Nephrol Date: 2007-10-17 Impact factor: 10.121
Authors: Saskia F Heeringa; Clemens C Möller; Jianyang Du; Lixia Yue; Bernward Hinkes; Gil Chernin; Christopher N Vlangos; Peter F Hoyer; Jochen Reiser; Friedhelm Hildebrandt Journal: PLoS One Date: 2009-11-10 Impact factor: 3.240
Authors: Andrea Kerti; Rózsa Csohány; Attila Szabó; Ottó Arkossy; Péter Sallay; Vincent Moriniére; Virginia Vega-Warner; Gábor Nyírő; Orsolya Lakatos; Tamás Szabó; Beata S Lipska; Franz Schaefer; Corinne Antignac; George Reusz; Tivadar Tulassay; Kálmán Tory Journal: Pediatr Nephrol Date: 2012-12-14 Impact factor: 3.714