Genetic Disorders of the Glomerular Filtration Barrier

Clin J Am Soc Nephrol. 2020 Dec 7;15(12):1818-1828. doi: 10.2215/CJN.11440919. Epub 2020 Mar 23.


The glomerular filtration barrier is a highly specialized capillary wall comprising fenestrated endothelial cells, podocytes, and an intervening basement membrane. In glomerular disease, this barrier loses functional integrity, allowing the passage of macromolecules and cells, and there are associated changes in both cell morphology and the extracellular matrix. Over the past 3 decades, there has been a transformation in our understanding about glomerular disease, fueled by genetic discovery, and this is leading to exciting advances in our knowledge about glomerular biology and pathophysiology. In current clinical practice, a genetic diagnosis already has important implications for management, ranging from estimating the risk of disease recurrence post-transplant to the life-changing advances in the treatment of atypical hemolytic uremic syndrome. Improving our understanding about the mechanistic basis of glomerular disease is required for more effective and personalized therapy options. In this review, we describe genotype and phenotype correlations for genetic disorders of the glomerular filtration barrier, with a particular emphasis on how these gene defects cluster by both their ontology and patterns of glomerular pathology.

Keywords: Kidney Genomics Series; endothelium; focal segmental glomerulosclerosis; glomerular basement membrane; glomerular filtration barrier; podocyte.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Endothelial Cells / pathology
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Glomerular Basement Membrane / pathology
  • Glomerular Filtration Barrier / pathology*
  • Glomerular Filtration Barrier / physiopathology
  • Glomerulonephritis / blood
  • Glomerulonephritis / genetics*
  • Glomerulonephritis / pathology
  • Glomerulonephritis / physiopathology
  • Humans
  • Phenotype
  • Podocytes / pathology
  • Risk Assessment
  • Risk Factors