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Children with MCD, although massively proteinuric, do not
have a generalized gbomerular leak to macromolecules ( 1 ). The
clearance of neutral macromolecules in MCD is actually less
than normal over a range of molecular radii. In contrast, the
clearance of anionic macromolecules is significantly increased.
This and several other lines of evidence suggest that protein-
uria results from a loss of the fixed negative charges of anionic
glycosaminoglycans in the glomerular capillary wall (1). The
mechanism by which these charges are lost has not been
defined. A highly cationic protein in the plasma and urine of
children with MCD has been recently described, but the patho-
genic significance of this protein has not been determined¡£
Edema
The traditional view has been that massive albuminuria in
NS causes a decrease in intravascular oncotic pressure, which
allows extravasation of fluid, resulting in hypovolemia, in-
creased aldosterone and antidiuretic hormone secretion, and
renal salt and water retention. Consistent with this mechanism
are the observations that, in MCD of childhood, edema seldom
occurs when serum albumin levels are above 2.0 g/dL and the
elevated hematocrit, prerenal azotemia, and fluid retention
during relapse may be improved by intravenous infusions of
salt-poor albumin.
Evidence against this model (2) includes the failure of some
patients to respond to intravenously administered albumin, the
fact that steroid-induced diuresis often occurs before a dra-
matic rise in serum albumin concentration, and the observa-
tions that plasma volumes are normal to increased and plasma
renin and aldosterone levels are decreased in many patients
with heavy proteinuria and edema. Finally. patients with con-
genital analbuminemia typically have little or no edema. An
alternative explanation for retention of salt and water in NS is
a decreased GFR, with a decreased filtration fraction.

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