Simulations of osmotic ultrafiltration failure in CAPD using a serial three-pore membrane/fiber matrix model

Abstract

Ultrafiltration failure (UFF) is a common complication of long-term peritoneal dialysis (PD). Functionally UFF is in most cases characterized by an enhanced peritoneal mass transfer area coefficient for glucose (PS(g)) combined with a largely unchanged peritoneal glucose osmotic conductance (L(p)Ssigma(g)). Morphologically, marked UFF occurs with fibrosis of the submesothelial zone in the peritoneum, combined with vasculopathy and vascular proliferation in deeper tissues. To computer simulate UFF, changes both in the vasculature and in the interstitium have to be taken into account. For that purpose, we used a three-pore membrane/fiber matrix serial barrier model, applying the three-pore model to the capillaries and the fiber-matrix model to the interstitium. The parameters of the three-pore model have been published previously. The interstitial fiber density was set at 0.5% (vol/vol) and the fiber radius (r(f)) at 6 A during control. If the interstitial fiber density was increased from 0.5 to 3%, and r(f) to 7.5 A (cf. collagen) while the capillary surface area was increased by 40% from control, then PS(g) increased from 9.3 to 11.5 ml/min, while the UF coefficient (L(p)S) was largely unchanged. Further increases in vascular surface area combined with further increases in fiber density caused further increments in PS(g), whereas L(p)S remained unchanged. It is concluded that a matrix of fibers coupled in series with a three-pore membrane may be used for simulating the pathophysiological alterations occurring in the peritoneum in UFF, explaining the commonly observed "uncoupling" of small solute transport (PS) from the peritoneal UF coefficient (L(p)S) in this condition.

Longitudinal Study of Small Solute Transport and Peritoneal Protein Clearance in Peritoneal Dialysis Patients

“…In addition, in the multivariate analysis of the peritonitis subgroups there was an association between membrane ultrafiltration capacity as well as PSTR in patients who had infections. Cause and effect cannot be inferred from this type of analysis, but this would be in line with more severe membrane injury causing reduced osmotic conductance and Pcl through more severe fibrosis (3,(20)(21)(22). This study's failure to detect a relationship between Pcl and comorbidity on multivariate analysis deserves comment.…”

Water transport across the peritoneal membrane

“…Solutes larger than glucose are hindered in their transport across the permeable pathways ("pores") of the capillary wall. The interstitium may also modify the transport of solutes across the peritoneal barrier, accounting for approximately 20-30% of the total diffusion resistance for a small solute (11). In the capillary wall (Fig.…”

“…Ultrafiltration failure in long-term PD is usually associated with an increment in small solute transport combined with reductions in the osmotic fluid transport across the peritoneum (11,29). These alterations are not compatible with just an "increased vascular surface area", i.e.…”

“…the glucose osmotic conductance (product of the peritoneal UF-coefficient, LpS, and the glucose reflection coefficient, ⌠g), and the rate of dissipation of the glucose osmotic gradient across the peritoneum during the dwell (30). By contrast, there seems to be an uncoupling between changes in the mass transfer area coefficient (MTAC) to glucose, and the changes occurring in LpS in these conditions (11). The unchanging, or even reduced, LpS in long-term PD has by some authors been attributed to reductions in AQP1-meditated water transport (31).…”

“…However, a more likely explanation for these changes is that a combination of two processes, namely i) increases in the vascularization of the peritoneum; and ii) the production of fibrotic scar tissue in the peritoneum, have occurred in parallel (2). It can be shown that a combination of these two processes will actually tend to reduce the osmotic conductance to glucose (mostly LpS, but also ⌠g) while the MTAC to glucose will tend to increase (due to increases in peritoneal capillary density) (11,30). In fact, overall, there is an increase, and not a reduction, in the abundance of AQP1 in the peritoneal membrane in typical ultrafiltration failure -as pointed in the detailed case study of Goffin et al (32).…”