The glomerular capillary wall functions as both a size-selective and charge-selective barrier.
Heparan sulfate is known to be an important component of the charge-selective barrier to filtration of
polyanions. We studied the alterations in both the charge and size selectivity barriers in a model of experimental
membranous nephropathy in the rabbit. The fractional clearance of both charged and uncharged
dextrans compared to
inulin was measured.
Sulfate incorporation into
glycosaminoglycans was measured and the glomerular
heparan sulfate was isolated and biochemically characterized.
Membranous nephropathy in the rabbit was induced with daily
injections of cationic
bovine serum albumin. After three weeks of injection animals had 735 +/- 196 mg/24 hours of
protein excretion. There was no change in [35S] incorporation in 24 hours by experimental animals, 440 +/- 91 DPM/mg dry weight of glomeruli, N = 9 versus 410 +/- 98, N = 11 in controls. The percentage of [35S] incorporated into
heparan sulfate versus
chondroitin sulfate was decreased, 60% +/- 3 versus 79% +/- 2, P less than 0.001.
Heparan sulfate from
membranous nephropathy eluted from ion exchange chromatography in a lower molarity
salt, indicating a lower effective charge. Fractional clearance of neutral
dextrans was significantly increased in
membranous nephropathy for
dextrans greater than 48 A, while fractional clearance of
dextran sulfates was significantly increased compared to controls for
dextrans greater than 32 A. Thus, in
membranous nephropathy there is loss of both charge selectivity and size selectivity. The loss of charge selectivity correlated with a change in the structure of the glomerular
heparan sulfate.(ABSTRACT TRUNCATED AT 250 WORDS)