Complexities of the glomerular basement membrane

Nat Rev Nephrol. 2021 Feb;17(2):112-127. doi: 10.1038/s41581-020-0329-y. Epub 2020 Aug 24.

Abstract

The glomerular basement membrane (GBM) is a key component of the glomerular capillary wall and is essential for kidney filtration. The major components of the GBM include laminins, type IV collagen, nidogens and heparan sulfate proteoglycans. In addition, the GBM harbours a number of other structural and regulatory components and provides a reservoir for growth factors. New technologies have improved our ability to study the composition and assembly of basement membranes. We now know that the GBM is a complex macromolecular structure that undergoes key transitions during glomerular development. Defects in GBM components are associated with a range of hereditary human diseases such as Alport syndrome, which is caused by defects in the genes COL4A3, COL4A4 and COL4A5, and Pierson syndrome, which is caused by variants in LAMB2. In addition, the GBM is affected by acquired autoimmune disorders and metabolic diseases such as diabetes mellitus. Current treatments for diseases associated with GBM involvement aim to reduce intraglomerular pressure and to treat the underlying cause where possible. As our understanding about the maintenance and turnover of the GBM improves, therapies to replace GBM components or to stimulate GBM repair could translate into new therapies for patients with GBM-associated disease.

Publication types

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

MeSH terms

  • Anti-Glomerular Basement Membrane Disease / etiology*
  • Diabetic Nephropathies / etiology*
  • Glomerular Basement Membrane / pathology*
  • Glomerular Basement Membrane / physiopathology*
  • Humans
  • Myasthenic Syndromes, Congenital / etiology*
  • Nephritis, Hereditary / etiology*
  • Nephrotic Syndrome / etiology*
  • Pupil Disorders / etiology*

Supplementary concepts

  • Pierson syndrome