A cellular model of human mesothelium to study the physiology of water transport during peritoneal dialysis and the biocompatibility of innovative glucose‐sparing solutions.

Abstract

The three pore model postulates that the endothelium of peritoneal capillaries is the major limiting barrier regulating water transport across peritoneal membrane during peritoneal dialysis (PD).We hypothesize that the mesothelium may represent an additional selective barrier to water diffusion in PD.We characterized an immortalized cell line of human mesothelium (HMC) to study the functional role of the water channel AQP1 expressed in vivo by mesothelial cells and also to test the biocompatibility of glucose‐sparing PD solutions containing xylitol and carnitine as the main osmotic agents.Transepithelial water transport was measured by TEA+‐sensitive microelectrodes. The biocompatibility of conventional versus innovative PD solutions was evaluated by MTT‐test, measurement of transepithelial electrical resistance (TEER) and production of pro‐inflammatory cytokines.HMCs showed polarized expression of Na+/K+‐ATPase and tight junctions markers but no endogenous expression of AQP1.HMC showed a low TEER compared to renal cells not expressing AQP1. However, the transepithelial water transport was comparable between the two cell types.Experiments in HMCs transfected with AQP1 cDNA, suggest that the water permeability of HMC is strictly dependent of the presence of AQP1.Biocompatibility assays indicate that conventional dialysis solutions with high glucose significantly reduce both cell viability and TEER, and increase pro‐inflammatory cytokines production.Interestingly, innovative PD solutions minimize these effects. These results suggest that the mesothelium may represent an additional selective barrier regulating water transport in PD. Importantly, we also demonstrated that the formulation of glucose‐sparing PD solutions containing xylitol and carnitine better preserve mesothelial cells viability and may represent a useful means to prolong the dialysis life of patients undergoing peritoneal dialysis.Support or Funding InformationApulian Region NATURe project Code: XUANRO4