Pediatric Nephrology

, Volume 23, Issue 6, pp 847–850

NPHS3: new clues for understanding idiopathic nephrotic syndrome

Editorial Commentary

DOI: 10.1007/s00467-008-0747-8

Cite this article as:
Hinkes, B.G. Pediatr Nephrol (2008) 23: 847. doi:10.1007/s00467-008-0747-8


Hereditary forms of childhood nephrotic syndrome (H-CHNS) have long been counted as rare variants of steroid-resistant nephrotic syndrome (SRNS). This concept must be specified by two new findings: First, a study on nephrotic syndrome manifesting in the first year of life documents that H-CHNS are actually the predominant cause of nephrotic syndrome in infants. Second, the recent identification of autosomal recessive nephrotic syndrome type 3 (NPHS3) caused by mutations in the phospholipase PLCE1 gene has, for the first time, shown steroid responsiveness in H-CHNS. NPHS3 is a severe form of isolated nephrotic syndrome with rapid progression to terminal renal failure. NPHS3 is caused by a developmental rather than structural podocyte dysfunction and is a major cause of diffuse mesangial sclerosis. Therapy response in NPHS3 is documented and could open insights into direct genomic and nongenomic effects of glucocorticoids on podocytes. The findings on NPHS3 support the idea that both clinical course and histology in H-CHNS are subject to genotypic variability and that mutational analysis is the most reliable diagnostic tool. Future studies are needed to determine the clinical implications of NPHS3. Identification of further variants of H-CHNS can be anticipated and may include steroid-responsive hereditary diseases.


Nephrotic syndrome NPHS3 Glucocorticoids 

Copyright information

© IPNA 2008

Authors and Affiliations

  1. 1.Klinik für Kinder und JugendlicheFriedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany
  2. 2.Department of PediatricsUniversity of Michigan, 8220C MSRB IIIAnn ArborUSA