Altered ultrastructural distribution of nephrin in minimal change nephrotic syndrome.
BACKGROUND
Nephrin is a cell-adhesion protein that is defective in congenital nephrotic syndrome of the Finnish type (CNF). Nephrin is synthesized by the podocytes and is localized to the slit membrane between individual foot processes of the podocytes. Although nephrin is apparently pivotal in the development of CNF, the role of nephrin in other causes of nephrotic syndrome is not fully understood.


METHODS
Renal biopsy specimens from patients with minimal change nephrotic syndrome (MCNS) were investigated. Nephrin distribution was studied with immunohistochemical and semiquantitative immunoelectron microscopic techniques and the results were related to the degree of foot process effacement found under the electron microscope.


RESULTS
In normal kidney, immunofluorescence revealed a linear staining along the capillary basement membranes, corresponding to the localization of nephrin in the slit membranes. In the biopsies from patients with MCNS, the nephrin pattern had become granular. The degree of granularization corresponded to the degree of foot process effacement. Ultrastructural semiquantification showed the amount of nephrin to be reduced both in areas with and without foot process effacement compared with the control specimens. The concentration of nephrin was lowest in the areas with foot process effacement and there was redistribution from the slits into the cytoplasm.


CONCLUSIONS
These findings demonstrate that nephrin expression is altered in MCNS. Whether this reflects a pathogenetic role for nephrin in MCNS or a phenomenon secondary to other causes of foot process effacement remains to be elucidated.
Wernerson
Annika
A
Department of Pathology, Karolinska Institutet, Huddinge University Hospital, Sweden. Annika.Wernerson@pathlab.hs.sll.se
Dunér
Fredrik
F
Pettersson
Erna
E
Widholm
Silwa Mengarelli
SM
Berg
Ulla
U
Ruotsalainen
Vesa
V
Tryggvason
Karl
K
Hultenby
Kjell
K
Söderberg
Magnus
M
D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007678:Kidney Glomerulus / Q000473:pathology* / Q000648:ultrastructure; D008565:Membrane Proteins; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000473:pathology*; D011506:Proteins / Q000032:analysis*
D008565:Membrane Proteins; D011506:Proteins; C113267:nephrin