Genetic causes of proteinuria and nephrotic syndrome: impact on podocyte pathobiology

Pediatr Nephrol. 2015 Feb;30(2):221-33. doi: 10.1007/s00467-014-2753-3. Epub 2014 Mar 2.


In the past 20 years, multiple genetic mutations have been identified in patients with congenital nephrotic syndrome (CNS) and both familial and sporadic focal segmental glomerulosclerosis (FSGS). Characterization of the genetic basis of CNS and FSGS has led to the recognition of the importance of podocyte injury to the development of glomerulosclerosis. Genetic mutations induce injury due to effects on the podocyte's structure, actin cytoskeleton, calcium signaling, and lysosomal and mitochondrial function. Transgenic animal studies have contributed to our understanding of podocyte pathobiology. Podocyte endoplasmic reticulum stress response, cell polarity, and autophagy play a role in maintenance of podocyte health. Further investigations related to the effects of genetic mutations on podocytes may identify new pathways for targeting therapeutics for nephrotic syndrome.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Humans
  • Nephrotic Syndrome / genetics*
  • Nephrotic Syndrome / pathology*
  • Podocytes / pathology*
  • Proteinuria / genetics*
  • Proteinuria / pathology*