We have analyzed glomerular sieving data from humans, rats in vivo, and fro
m isolated perfused rat kidneys (IPK) and present a unifying hypothesis tha
t seems to resolve most of the conflicting results that exist in the litera
ture. Particularly important are the data obtained in the cooled IPK, becau
se they allow a variety of experimental conditions for careful analysis of
the glomerular barrier; conditions that never can be obtained in vivo. The
data strongly support the classic concept of a negative charge barrier, but
separate components seem to be responsible for charge and size selectivity
. The new model is composed of a dynamic gel and a more static membrane lay
er. First, the charged gel structure close to the blood compartment has a c
harge density of 35-45 meq/l, reducing the concentration of albumin to 5-10
% of that in plasma, due to ion-ion interactions. Second, the size-selectiv
e structure has numerous functional small pores (radius 45-50 Angstrom) and
far less frequent large pores (radius 75-115 Angstrom), the latter account
ing for 1% of the total hydraulic conductance. Both structures are required
for the maintenance of an intact glomerular barrier.