The current understanding of glomerular ultrafiltration reveals that there is little resistance to flow after filtrate has traversed the glomerular basement membrane (GBM) and overlying slit diaphragms and entered the Bowman’s space (BS). Fluid filters between the foot processes into BS or into the space between the glomerular parietal and visceral epithelial cells and the glomerular barrier.

We have reconstructed podocytes (visceral epithelial cells) and underlying GBM using micrographs of ultrathin (100 nm) serial sections of Wistar rat kidney (humanely killed by cervical dislocation) and human kidney (obtained at nephrectomy) with ethics committee approval and informed consent. In rat glomeruli an initial survey of the filtration barrier revealed that while the majority of filtration slits between foot processes open directly into the BS (66 ± 7 %, mean ± S.E.M., range 20-80 %), the remainder open into the space between the podocyte cell body and GBM. Full reconstruction of the podocyte and sub-podocyte space (SPS) showed that some processes which anchor the cell to the GBM form pores (0.6 ± 0.2 µm diameter, n = 5) which connect the Swith BS. Other reconstructed podocyte pores form very narrow channels (0.16 ± 0.03 µm wide, n = 6) connecting the Sto BS. The open area of the pores/channels connecting Sto BS is 0.25-0.5 % of the GBM area draining into the SPS. Initial results on human glomeruli show similar findings.

The sub-podocyte space sandwiched between the podocyte and the GBM may enable more effective transduction of fluid flux by the podocyte and control of local ultrafiltration via podocytic pores and/or slit diaphragms. In addition, it is possible that the podocytic contractile state may exert an active control over the efflux of fluid from the filtration slits into the BS via the SPS. The functional significance of the Shas yet to be determined.

This work was funded by The Wellcome Trust (58083) and B.H.F(BB2000003).