Can the Three Pore Model Correctly Describe Peritoneal Transport of Protein?

Abstract

The three pore model (3PM) includes large pores for the description of protein leak to the peritoneal cavity during peritoneal dialysis. However, the reliability of this description has been not fully tested against clinical data yet. Peritoneal transport parameters were estimated using 3PM, extended 3p model (with estimation of fraction of large pores, ext3PM), ext3PM with modified size of pores and proteins (mext3PM), and simplified two pore (2PM, small and ultrasmall pores) models for 32 patients on peritoneal dialysis investigated using the sequential peritoneal equilibration test (consecutive peritoneal equilibration test [PET]: glucose 2.27%, 4 h, and miniPET: glucose 3.86%, 1 h). Urea, creatinine, glucose, sodium, phosphate, albumin, and IgM concentrations were measured in dialysis fluid and plasma. Ext3PM and mext3PM, with large pore fraction of about 0.14, provided a good description of fluid and small solute kinetics, but their predictions for albumin transport were less accurate. Two pore model precisely described the data on fluid and small solute transport. The 3p models could not describe the diffusive-convective transport of albumin as precisely as the transport of fluid, small solutes, and IgM. The 2p model (not applicable for proteins) was an efficient tool for modeling fluid and small solute transport.

Peritoneal Fluid Transport rather than Peritoneal Solute Transport Associates with Dialysis Vintage and Age of Peritoneal Dialysis Patients

“…The degree of generality and sophistication of transport models span from simple membrane models [ 8 ], through the three-pore (3p) or two-pore (2p) models [ 9 – 11 ], to the spatially distributed models [ 12 – 17 ]. The pore models of peritoneal fluid and solute transport may explain some seemingly puzzling phenomena, such as the discrepancy between the substantial sieving of small solutes and the low efficiency of low molecular osmotic agents (as glucose) expressed by the reflection coefficient, and were successfully applied for mathematical modeling of peritoneal transport [ 9 , 18 – 26 ].…”

“…The pore models of peritoneal fluid and solute transport may explain some seemingly puzzling phenomena, such as the discrepancy between the substantial sieving of small solutes and the low efficiency of low molecular osmotic agents (as glucose) expressed by the reflection coefficient, and were successfully applied for mathematical modeling of peritoneal transport [ 9 , 18 – 26 ]. Except for the Personal Dialysis Capacity method [ 20 , 27 , 28 ], these models have in general not been applied for the estimation of parameters for individual patients, but, with the advent of the sequential peritoneal equilibration test (sPET), based on a simple clinical protocol, it is possible to estimate pore model parameters in individual patients [ 11 , 26 ].…”

“…Using sPET and applying the 2p model, one may focus on fluid and small solute transport by assuming only two types of pores, ultrasmall and small pores [ 11 ], thus leaving out the third type of pores, large pores, through which according to 3p model macromolecules leak from blood to the peritoneal cavity [ 9 , 29 ]. In this sPET plus 2p modeling approach, protein clearances are considered to be observational indices as they are not assessed by the 2p model [ 11 ]. Furthermore, the 3p model may not correctly describe the absorption of macromolecular volume markers from the peritoneal cavity and the effect of convective transport on albumin clearance [ 11 , 22 ].…”

“…In this sPET plus 2p modeling approach, protein clearances are considered to be observational indices as they are not assessed by the 2p model [ 11 ]. Furthermore, the 3p model may not correctly describe the absorption of macromolecular volume markers from the peritoneal cavity and the effect of convective transport on albumin clearance [ 11 , 22 ].…”

“…The aim of the current study was to explore to what extent changes of directly measured observational indices may reflect modifications of the pore system occurring with ageing of the peritoneal membrane related to advancing age of the patients and time on PD. For this purpose we estimated parameters of the 2p model, using data from sPET [ 11 , 26 ], and investigated associations (1) between model parameters versus patient age and dialysis vintage, (2) between observational indices and estimated model parameters, and (3) between the model parameters themselves.…”