Sieve plugs in fenestrae of glomerular capillaries--site of the filtration barrier?

The exact location of the filtration barrier of the glomerular capillary wall, which consists of an endothelium, a basement membrane and a visceral epithelium, has not yet been determined. Apparent discrepancies between different investigators in the past could be explained if postmortem artifactual tissue changes, due to subnormal blood pressure or anoxia, have taken place in the endothelium before the tissue and tracers have been sufficiently fixed and immobilized by the fixative. To test this supposition, a new method of fixation, which includes a technique to maintain a physiological perfusion pressure and a fixative composed of an oxygen-carrying blood substitute fluid containing glutaraldehyde, was employed combined with contrast enhancement. New observations of the glomerular capillary wall revealed that filamentous plugs (about 90 nm in height) filled the capillary fenestrae and a filamentous surface coat about 60 nm thick covered the interfenestral domains of the endothelial cell. Based on these purely morphological data, we dare to suggest that the fenestral plugs are the primary site of the glomerular filtration barrier - albeit highly speculative, nevertheless a logical location - and consequently that the glomerular filtration process is a 'tangential-flow' as opposed to a 'dead-end' filtration process. A tangential-flow filtration would minimize 'clogging' and 'concentration polarization' in the 'filter'. Copyright 2002 S. Karger AG, Basel