Rapid Response to Cyclosporin A and Favorable Renal Outcome in Nongenetic Versus Genetic Steroid–Resistant Nephrotic Syndrome

• Published in: Clinical journal of the American Society of Nephrology Vol. 11; no. 2; pp. 245 - 253
• Main Authors: Büscher, Anja K., Beck, Bodo B., Melk, Anette, Hoefele, Julia, Kranz, Birgitta, Bamborschke, Daniel, Baig, Sabrina, Lange-Sperandio, Bärbel, Jungraithmayr, Theresa, Weber, Lutz T., Kemper, Markus J., Tönshoff, Burkhard, Hoyer, Peter F., Konrad, Martin, Weber, Stefanie
• Format: Journal Article
• Language: English
• Published: United States American Society of Nephrology 05.02.2016
• Subjects: Adolescent; Austria; Biopsy; Child; Child, Preschool; Cross-Sectional Studies; Cyclosporine - adverse effects; Cyclosporine - therapeutic use; Disease Progression; DNA Mutational Analysis; Female; Genetic Predisposition to Disease; Germany; Humans; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; Infant; Intracellular Signaling Peptides and Proteins - genetics; Kidney - drug effects; Kidney - pathology; Kidney - physiopathology; Kidney Failure, Chronic - diagnosis; Kidney Failure, Chronic - genetics; Longitudinal Studies; Male; Membrane Proteins - genetics; Mutation; Nephrotic Syndrome - congenital; Nephrotic Syndrome - diagnosis; Nephrotic Syndrome - drug therapy; Nephrotic Syndrome - genetics; Nephrotic Syndrome - physiopathology; Original; Phenotype; Recovery of Function; Remission Induction; Risk Factors; Time Factors; Treatment Outcome; WT1 Proteins - genetics; kidney failure, chronic; mutation; cyclosporine A; NPHS1; steroid resistant nephrotic syndrome; NPHS2; WT1; FSGS; humans
• ISSN: 1555-9041; 1555-905X; 1555-905X
• DOI: 10.2215/CJN.07370715

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. 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. 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. 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.