Glomerular perm-selective function

Abstract

The glomerular capillary wall functions as an efficient barrier that restricts the passage of plasma proteins and allows a high flow rate of filtration for plasma water and small solutes. Experimental studies have confirmed the theoretical predictions that circulating macromolecules are retained within the lumen of glomerular capillaries because of their size, shape and electrical charge [1–6]. The selective function of the glomerular capillary wall allows an almost complete restriction of large proteins and albumin while low molecular weight proteins are almost freely filtered and reabsorbed at tubular level [7, 8]. Glomerular permeability to circulating macromolecules has been extensively studied in the last few years, both by experimental studies and clinical investigations, with the aim of elucidating the mechanisms by which the glomerular membrane loses its selective function during development of most glomerular diseases. More recently additional interest in this area has been generated by the observation that the use of angiotensin converting enzyme (ACE) inhibitors in experimental models of glomerular dysfunction and in patients, beside reducing blood pressure, prevents or lessens urinary protein excretion. Experimental research in this field has focused on the mechanisms by which such pharmacological treatment can restore, at least partially, the selective function of the glomerular barrier [9–12]. The objective of this communication is to review some recent developments in experimental and clinical research on glomerular selectivity that illustrate new aspects of the glomerular charge- and size-selective function. In particular, recent studies are reviewed that indicate the distribution of restrictive sites on the glomerular basement membrane (GBM) to the filtration of albumin. Since recent evidence indicates that epithelial cells, in addition to GBM, exert a major role in determining the selective function of the glomerular capillary wall, other studies are discussed which aimed to clarify whether there was a correlation between changes in permselective function and quantification of structural changes of glomerular cells as assessed using morphometrical techniques. Observations on the filtration of test macromolecules with different configuration are also presented since they provide new insights on the efiFects of molecular configuration on the filtration of test macromolecules. Theoretical analysis of experimental results obtained with these test macromolecules has been carried out to determine membrane permeability parameters in both the normal state and in a model of glomerular injury in the rat. Both theoretical analyses are reviewed because they indicate that glomerular size-selective function is more restrictive than that estimated previously by experimental and human studies.