Biocompatibility of icodextrin

Abstract

Peritoneal dialysis (PD) has been a successful form of As a result of the growing awareness of the potential chronic renal replacement therapy for more than twenty effects of glucose-based solutions on membrane physiolyears. In spite of the successes of this therapy, there is ogy, there has been an increased emphasis on the devela growing awareness that the high glucose content of PD opment of second-generation PD solutions that reduce solutions may ultimately compromise membrane perforor eliminate glucose exposure and are more biocompatimance over time, a realization that underlies the search ble with membrane biological and metabolic processes for, and production of, glucose-free solutions. Icodextrin, [30–34]. one of the second-generation PD solutions, was develThe biocompatibility of a PD solution can be defined oped as an alternative to glucose-based solutions to proas the ability of a solution formulation to permit longvide a sustained level of ultrafiltration through the use term dialysis without any clinically significant changes of a glucose polymer as the osmotic agent, and is curin the functional characteristics of the peritoneum and, rently used by more than 9000 patients worldwide. While as such, is of paramount importance not only in mainicodextrin has now proven itself to be clinically useful taining the health of the membrane, but also in permitin the fluid management of PD patients, there are indicating PD to be a successful long-term therapy. The potentions that it also may demonstrate improved biocompatitial role of PD solution biocompatible factors in clinical bility when compared to the traditional solutions. This outcomes is illustrated in Figure 1. Solution components review evaluates the biocompatibility of icodextrin vercan affect leukocyte, mesothelial cell, endothelial cell, and sus glucose-based solutions, and shows how this new fibroblast function, resulting in alterations in cytokine, solution may significantly contribute to an overall therachemokine, and growth factor networks, up-regulation peutic strategy for improving PD. of pro-inflammatory and profibrotic pathways, impaired peritoneal host defense, and the induction of carbonyl and oxidative stress. Such perturbations of normal physiBIOCOMPATIBILITY ology have been proposed as causative factors contributThe peritoneal membrane is a complex tissue that ing to changes in peritoneal structure, such as peritoneal plays a pivotal role in peritoneal cavity homeostasis [1]. fibrosis, sclerosis and vasculopathy, and changes in periThe cellular components of the membrane are active toneal function, including increased solute permeability in host defense [2–5], maintain a balance of peritoneal and ultrafiltration (UF) failure. coagulant and fibrinolytic activity [6–9], contribute to The characteristics of conventional glucose-based dialmembrane repair and remodeling of the extracellular ysis solutions that have been reported to affect the biomatrix [10, 11], and regulate cytokine and chemokine compatibility of the formulation include the pH/buffer production (Table 1) (abstract; Jorres et al, Nephrol Dial system, the osmolarity, the glucose concentration, and Transplant 8:1023, 1993) [12–15]. The membrane itself the glucose degradation product (GDP) profile of that functions as a semipermeable barrier regulating the sesolution. Icodextrin is virtually identical to glucose-based lective transport of water and solutes between the sysPD solutions in its formulation except for the replacetemic circulation and the peritoneal cavity during PD. ment of glucose with icodextrin as the osmotic agent It is becoming increasingly apparent that, in spite of the (Table 2). Icodextrin is a high molecular weight glucose success of PD as a renal replacement therapy, chronic polymer fraction of hydrolyzed corn starch. Briefly, it is exposure to glucose-based solutions may compromise a mixture of d-glucopyranose polymers of different chain the biological function of the peritoneal membrane [28, 29]. lengths, between 4 and 250 units, linked by -(1-4) and -(1-6) glucosidic bonds, exhibiting a mean molecular weight of 16,200 Daltons (D). The chemical properties