Role Oftranscellularwater Channels in Peritoneal Dialysis

Abstract

A ccording to the three-pore model of peritoneal transport (1-3), the endothelium of the perito neal and mesenteric capillaries represents a major barrier to trans peritoneal solute permeation and to water flow in peritoneal dialysis (PD). The chief transcapillary exchange route for water and small solutes seems to be represented by the clefts between endothelial cells, commonly denoted "small pores" and having a functional radius of 40 A -50 A (4,5). These pathways are generally protein-restrictive, although albumin can, to some extent, diffuse across them. The passage of proteins larger than albumin from blood to peritoneum seems to be confined to so-called "large pores" of radius 200 A -300 A, which are most likely modified and widened interendothelial clefts (6,7). Across small pores, a nearly complete balance exists between hydraulic and colloid osmotic pressures (the socalled "Starling forces"). Thus, despite the presence of a very large number of small pores, only a very slow fluid ultrafiltration (UF) occurs through these pores under normal conditions. Across large pores, colloid osmotic forces are negligible (6). Here, macromolecules pass unidirectionally, by filtration (convection), from blood to peritoneum, more or less independent of the net fluid flow occurring through small pores. Although the large pores constitute only 0.01% of the total population of pores, plasma filtering through these pores normally makes up a considerable portion of the total net transcapillary UF (6,7). Approximately 10 years ago, we pointed to the importance of a third porous pathway, of special importance in PD, namely a "water-only" trans cellular pathway that rejects solute transport, but that sensitively responds to crystalloid osmotic forces (1). Water-only pores were postulated to account for nearly one half