Glomerular albumin leakage and morphology after neutralization of polyanions. II. Discrepancy of protamine induced albuminuria and fine structure of the glomerular filtration barrier.

Changes in the fine structure of the glomerular filtration barrier were studied by perfusion of isolated rat kidneys with varying doses of protamine: 1) at low doses (110-150 micrograms/ml) ultrastructural changes were only detectable after prolonged recirculation (90-120'), 2) at high doses (250-330 micrograms/ml) profound epithelial foot process lesions were observed even after a short perfusion time, 3) at any concentration protamine particles were distributed in the laminae rarae of the GBM, thus visualizing neutralization of fixed negative charges. Reduction of glomerular anionic sites caused pronounced albuminuria even before podocyte morphological alterations were detectable. The effects of protamine on structure and function of the glomerular capillary wall are dose and time dependent. Besides intact morphology of the epithelial cells regular distribution of negative charges is necessary to maintain glomerular barrier function to macromolecules. Foot process alterations are not the primary reason for increased proteinuria but rather a secondary phenomenon.