Pathophysiology of Peritoneal Membrane Failure

Abstract

Correspondence to: R.T. Krediet, Division of Nephrology, Department of Medicine, Academic Medical Center, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. Various mathematical models have been used for the assessment of the peritoneum as a dialysis membrane, for example, membrane models and distributed models. These have been discussed by Lysaght and Farrel (1) and by Waniewski (2). The present review is based on the three-pore model (3–5). The peritoneal membrane, as used for peritoneal dialysis (PD), can be divided into three parts for the purpose of simplicity. These are the mesothelium, the interstitial tissue, and the microvessels present in the interstitial tissue. It is unlikely that the mesothelium is an important barrier to solute transport because no osmotic pressure gradient across it was found during PD in rats (6). The barrier function of interstitial tissue is not very well known. Using in vivo microscopy of the rat mesentery, a size-selective restriction in the transport of macromolecules was detected and has been reported (7). More recent studies comparing the transport properties of liver peritoneum (almost no interstitial tissue) with that of parietal peritoneum were unable to show differences (8,9). The capillary wall is probably the most important structure. Solute transport across it is generally considered to occur through a system of pores (10,11). This process occurs mainly through a large number of small pores (radius 40 – 50 A), probably represented by paracellular clefts in the endothelium, together with a very low number of large pores (radius approximately 250 A), allowing transport of macromolecules from blood to peritoneum. In addition, an abundance of water-conductive “ultrasmall pores” (radius approximately 3 – 5 A) in the plasmalemma has been assumed, allowing water transport but rejecting the transfer of solutes (3–5). It has been made plausible that aquaporins, and especially aquaporin–1, are the proteins constituting these transendothelial water channels (12–14). For high glucose concentrations (3.86%/4.25%) in dialysis fluid, the three-pore model predicted approximately one half of transperitoneal ultrafiltration (UF) would occur through aquaporins, with the other half through small pores.