Clinical course and NPHS2 analysis in patients with late steroid-resistant nephrotic syndrome

• Published in: Pediatric nephrology (Berlin, West) Vol. 23; no. 2; pp. 251 - 256
• Main Authors: Schwaderer, Peter, Knüppel, Tanja, Konrad, Martin, Mehls, Otto, Schärer, Karl, Schaefer, Franz, Weber, Stefanie
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.02.2008; Springer; Springer Nature B.V
• Subjects: Biopsy; Child; Child, Preschool; Cyclophosphamide - therapeutic use; Cyclosporine - therapeutic use; DNA Mutational Analysis; Drug Resistance; Drug Therapy, Combination; Female; Glomerulosclerosis, Focal Segmental - drug therapy; Glomerulosclerosis, Focal Segmental - pathology; Glucocorticoids - therapeutic use; Humans; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Kidney diseases; Male; Medicine; Medicine & Public Health; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mutation; Nephrology; Nephrotic Syndrome - drug therapy; Nephrotic Syndrome - genetics; Nephrotic Syndrome - pathology; Original Article; Patients; Pediatrics; Remission Induction; Steroids; Urology; Germany; Late steroid resistance; gene; MC; Late nonresponder; FSGS; Steroid resistance; Podocin
• ISSN: 0931-041X; 1432-198X
• DOI: 10.1007/s00467-007-0653-5

A small fraction of patients with initial steroid-sensitive nephrotic syndrome (SSNS) develops late steroid resistance, i.e. a lack of remission after 4 weeks of relapse treatment despite previous response to steroids. The pathophysiological basis of late resistance and the long-term prognosis remain obscure. Fourteen out of 360 patients with SSNS who were seen in our department between 1954 and 2005 developed late resistance. Median age at onset of NS was 4 years and median duration of development of late resistance 4.6 months. Histology showed minimal-change (MC) nephropathy in six patients and focal segmental glomerulosclerosis (FSGS) in three patients on initial biopsy and four patients on repeat biopsies. Late resistance was treated with cyclophosphamide in five patients, cyclosporine A in three, and both drugs in one. Eight of these nine patients went into remission. All 14 patients maintained a stable kidney function during their period of observation. NPHS2 mutation analysis in eight patients revealed no pathogenic mutations, suggesting that late resistance is not typically associated with mutations in the NPHS2 gene. With respect to the clinical course, late resistance appears to resemble SSNS and is characterized by a favorable outcome.