Kinetic Analysis of Peritoneal Fluid and Solute Transport with Combination of Glucose and Icodextrin as Osmotic Agents

Abstract

Controlling extracellular volume and plasma sodium concentration are two crucial objectives of dialysis therapy, as inadequate sodium and fluid removal by dialysis may result in extracellular volume overload, hypertension, and increased cardiovascular morbidity and mortality in end-stage renal disease patients. A new concept to enhance sodium and fluid removal during peritoneal dialysis (PD) is the use of dialysis solutions with two different osmotic agents. To investigate and compare, with the help of mathematical modeling and computer simulations, fluid and solute transport during PD with conventional dialysis fluids (3.86% glucose and 7.5% icodextrin; both with standard sodium concentration) and a new combination fluid with both icodextrin and glucose (CIG; 2.6% glucose/6.8% icodextrin; low sodium concentration). In particular, this paper is devoted to improving mathematical modeling based on critical appraisal of the ability of the original three-pore model to reproduce clinical data and check its validity across different types of osmotic agents. Theoretical investigations of possible causes of the improved fluid and sodium removal during PD with the combination solution (CIG) were carried out using the three-pore model. The results of computer simulations were compared with clinical data from dwell studies in 7 PD patients. To fit the model to the low net ultrafiltration (366+/-234 mL) obtained after a 4-hour dwell with 3.86% glucose, some of the original parameters proposed in the three-pore model (Rippe & Levin. Kidney Int 2000; 57:2546-56) had to be modified. In particular, the aquaporin-mediated fractional contribution to hydraulic permeability was decreased by 25% and small pore radius increased by 18%. The simulations described well clinical data that showed a dramatic increase in ultrafiltration and sodium removal with the CIG fluid in comparison with the two other dialysis fluids. However, to adapt the three-pore model to the selected group of PD patients (fast transporters with small ultrafiltration capacity on average), the peritoneal pore structure had to be modified. As the mathematical model was capable of reproducing the clinical data, this shows that the enhanced ultrafiltration with the combination fluid is caused by the additive effect of the two different osmotic agents and not by a specific impact of the new dialysis fluid on the transport characteristics of the peritoneum.