Rapid response to cyclosporin A and favorable renal outcome in nongenetic versus genetic steroid-resistant nephrotic syndrome

• Verfasst von: Büscher, Anja K. [VerfasserIn]
• Verfasst von: Beck, Bodo B. [VerfasserIn]
• Verfasst von: Melk, Anette [VerfasserIn]
• Verfasst von: Hoefele, Julia [VerfasserIn]
• Verfasst von: Kranz, Birgitta [VerfasserIn]
• Verfasst von: Bamborschke, Daniel [VerfasserIn]
• Verfasst von: Baig, Sabrina [VerfasserIn]
• Verfasst von: Lange-Sperandio, Bärbel [VerfasserIn]
• Verfasst von: Jungraithmayr, Theresa [VerfasserIn]
• Verfasst von: Weber, Lutz T. [VerfasserIn]
• Verfasst von: Kemper, Markus J. [VerfasserIn]
• Verfasst von: Tönshoff, Burkhard [VerfasserIn]
• Verfasst von: Hoyer, Peter F. [VerfasserIn]
• Verfasst von: Konrad, Martin [VerfasserIn]
• Verfasst von: Weber, Stefanie [VerfasserIn]
• Titel: Rapid response to cyclosporin A and favorable renal outcome in nongenetic versus genetic steroid-resistant nephrotic syndrome
• Verf.angabe: Anja K. Büscher, Bodo B. Beck, Anette Melk, Julia Hoefele, Birgitta Kranz, Daniel Bamborschke, Sabrina Baig, Bärbel Lange-Sperandio, Theresa Jungraithmayr, Lutz T. Weber, Markus J. Kemper, Burkhard Tönshoff, Peter F. Hoyer, Martin Konrad, and Stefanie Weber for the German Pediatric Nephrology Association (GPN)
• E-Jahr: 2016
• Jahr: r2015
• Umfang: 9 S.
• Fussnoten: Accepted October 30, 2015 ; Gesehen am 24.04.2020
• Titel Quelle: Enthalten in: American Society of NephrologyClinical journal of the American Society of Nephrology
• Ort Quelle: Washington, DC : American Society of Nephrology, 2006
• Jahr Quelle: 2016
• Band/Heft Quelle: 11(2016), 2, Seite 245-253
• ISSN Quelle: 1555-905X
• DOI: doi:10.2215/CJN.07370715
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: cyclosporine A
• Sach-SW: FSGS
• Sach-SW: humans
• Sach-SW: kidney failure, chronic
• Sach-SW: mutation
• Sach-SW: NPHS1
• Sach-SW: NPHS2
• Sach-SW: steroid resistant nephrotic syndrome
• Sach-SW: WT1
• K10plus-PPN: 1696124042

Abstract

Background and objectives Treatment of congenital nephrotic syndrome (CNS) and steroid-resistant nephrotic syndrome (SRNS) is demanding, and renal prognosis is poor. Numerous causative gene mutations have been identified in SRNS that affect the renal podocyte. In the era of high-throughput sequencing techniques, patients with nongenetic SRNS frequently escape the scientific interest. We here present the long-term data of the German CNS/SRNS Follow-Up Study, focusing on the response to cyclosporin A (CsA) in patients with nongenetic versus genetic disease. - Design, setting, participants, & measurements Cross-sectional and longitudinal clinical data were collected from 231 patients with CNS/SRNS treated at eight university pediatric nephrology units with a median observation time of 113 months (interquartile range, 50-178). Genotyping was performed systematically in all patients. - Results The overall mutation detection rate was high at 57% (97% in CNS and 41% in SRNS); 85% of all mutations were identified by the analysis of three single genes only (NPHS1, NPHS2, and WT1), accounting for 92% of all mutations in patients with CNS and 79% of all mutations in patients with SRNS. Remission of the disease in nongenetic SRNS was observed in 78% of patients after a median treatment period of 2.5 months; 82% of nongenetic patients responded within 6 months of therapy, and 98% of patients with nongenetic SRNS and CsA-induced complete remission (normalbuminemia and no proteinuria) maintained a normal renal function. Genetic SRNS, on the contrary, is associated with a high rate of ESRD in 66% of patients. Only 3% of patients with genetic SRNS experienced a complete remission and 16% of patients with genetic SRNS experienced a partial remission after CsA therapy. - Conclusions The efficacy of CsA is high in nonhereditary SRNS, with an excellent prognosis of renal function in the large majority of patients. CsA should be given for a minimum period of 6 months in these patients with nongenetic SRNS. In genetic SRNS, response to CsA was low and restricted to exceptional patients.