The glomerular basement membrane charge-selectivity barrier: an oversimplified concept?

The precise nature and role of a charge-selectivity barrier, existing at the level of the glomerular capillary wall has been the subject of continuing controversy since it was first postulated over 30 years ago. Recent studies suggest that some earlier observations may have been overinterpreted and that the conclusions reached should be re-examined. The concept of a charge-selectivity barrier at the level of the glomerular filtration membrane which influences the permeation of circulating plasma proteins, dependent upon their charge, became widely accepted during the 1970s and 1980s [1,2]. Evidence was derived from investigations in which anionic sites were detected histochemically using various cationic tracers, and the demonstration that anionic component removal by specific enzymes or their neutralization by polycations resulted in increased glomerular permeability. Despite the contribution of epithelial and endothelial cell surface sialoglycoproteins (podocalyxin) to glomerular capillary wall anionic charge [3], and the demonstration of hyaluronan [4] and chondroitin sulphate proteoglycans [5] in the GBM and mesangial matrix, the principal charge barrier was conceived to comprise of a linear array of anionic sites associated with heparan sulphate proteoglycan (HS-PG) networks in the laminae rarae of the glomerular basement membrane (GBM).