Theoretical analysis of osmotic agents in peritoneal dialysis. What size is an ideal osmotic agent?

Abstract

In this article the difference between osmotic fluid flow (ultrafiltration) as driven by osmotic pressure and diffusion through thin leaky membranes is discussed. It is pointed out that water transport induced by osmosis is fundamentally different from the process of water diffusion. Applying modern hydrodynamic pore theory, the molar solute concentration and the solute concentration in grams per 100 mL, exerting the same initial transmembrane osmotic pressure as a 1% glucose solution, was investigated as a function of solute molecular weight (MW). It was then assumed, base on experimental data, that the major pathway responsible for the peritoneal osmotic barrier characteristics is represented by pores of radius approximately 47 A. With increasing solute radius, the osmotic reflection coefficient (sigma) and, hence, the osmotic efficiency per mole of solute will increase. However, simultaneously, the molar concentration per unit solute weight will decrease. The balance point between these two events apparently occurs at a solute MW of approximately 1 kDa. An additional advantage of using solutes of high MW as osmotic agents during peritoneal dialysis (PD), rather than increased osmotic efficiency per se, lies in the fact that large solutes, due to their low peritoneal diffusion capacity, will maintain a sustained rate of ultrafiltration (osmosis) over a prolonged period. To illustrate this, we have performed computer simulations of peritoneal fluid transport according to the three-pore model of peritoneal permselectivity. According to these simulations, 4% of an 800 Da polymer solution (+50 mmol/L above isotonicity) will produce the same cumulative amount of intraperitoneal fluid volume ultrafiltered (UF) during 360-400 minutes as 4% of a 2 kDa polymer solution (+20 mmol/L) or 6.5% of a 10 kDa polymer solution (+6.5 mmol/L) having the same electrolyte concentration as dialysis solutions conventionally used for PD. Similar cumulative UF volumes (during 400 minutes) can be obtained by a 2.5% glycerol (+272 mmol/L) or a 3.2% glucose-containing dialysis solution (+177 mmol/L) with conventional electrolyte composition.