Genetic kidney diseases disclose the pathogenesis of proteinuria

Citation
H. Jalanko et al., Genetic kidney diseases disclose the pathogenesis of proteinuria, ANN MED, 33(8), 2001, pp. 526-533
Citations number
86
Language
INGLESE
art.tipo
Article
Categorie Soggetti
General & Internal Medicine","Medical Research General Topics
Journal title
ANNALS OF MEDICINE
ISSN journal
0785-3890 → ACNP
Volume
33
Issue
8
Year of publication
2001
Pages
526 - 533
Database
ISI
SICI code
0785-3890(200111)33:8<526:GKDDTP>2.0.ZU;2-W
Abstract
The sieving of plasma components occurs in the kidney through the glomerula r capillary wall. This filter is composed of three layers; endothelium, glo merular basement membrane (GBM), and podocyte foot processes connected by s lit diaphragms. Defects in this barrier lead to proteinuria and nephrotic s yndrome. Previously, defective GBM was regarded to be responsible for prote inuria. However, recent work on genetic diseases has indicated that podocyt es and the slit diaphragm are crucial in restricting protein leakage. Conge nital nephrotic syndrome of the Finnish type (NPHS1) is caused by mutations in a novel NPHS1 gene, which encodes for a cell adhesion protein, nephrin. This protein is synthesized by podocytes, and seems to be a major componen t of the slit diaphragm. In severe NPHS1, lack of nephrin leads to missing slit diaphragm. The role of nephrin in acquired kidney diseases remains unk nown. In addition to nephrin, other podocyte proteins (podocin, alpha -acti nin-4, CD2AP, FAT) have recently been identified and associated with the de velopment of proteinuria. It seems that the slit diaphragm and its interpla y with the podocyte cytoskeleton is critical for the normal sieving process , and defects in one of these components easily lead to proteinuria.