Metabolic and laboratory effects of icodextrin

Abstract

The osmotic agents used in peritoneal dialysis solu- major factors: first, the influence of the polymer size on tions are not metabolically inert and systemic absorption absorption rates (and consequently systemic carbohyof these agents results in metabolic alterations that may drate load), and second, the temporal delay introduced have clinically meaningful consequences [1‐4]. The use by the metabolic steps necessary for the breakdown of of glucose, the most common osmotic agent in peritoneal the carbohydrate polymers to glucose. As addressed elsedialysis solutions, has been associated with a variety of where in this Supplement issue, icodextrin absorption metabolic consequences ranging from acute hyperglyce- from the peritoneal cavity occurs predominantly via conmia and hyperinsulinemia to dyslipidemia and weight vective pathways (such as, lymphatics) and hence is limgain. Replacement of glucose by glucose polymers [5‐11] ited despite the prolonged dwell time. As important, howand non-carbohydrate-based osmotic agents (such as ever, is the temporal profile of metabolism of the icodextrin amino-acids) [2, 12‐18] is expected to result in metabolic polymers to glucose. Very little metabolism of icodextrin profiles distinct from those observed with glucose either polymers occurs in the peritoneal cavity in humans, and because of the avoidance of the glucose-dependent ef- this metabolism tends to be limited to a reduction in fects or because of aspects peculiar to these novel os- the concentration of larger polymers with resultant rise motic agents. In the case of icodextrin both of these in the concentrations of smaller polymers; however, little attributes apply, and it is the intent of this article to if any glucose is released intraperitoneally. Therefore, review the metabolic changes and contrast them with from the standpoint of the peritoneal membrane and its what is observed with dextrose. component cells, icodextrin is functionally a “non-gluIn addition, we present a review of laboratory changes cose” osmotic agent [1]. After absorption into the sysassociated with icodextrin use. These include laboratory temic circulation, icodextrin polymers are metabolized changes thought to be associated with systemic levels of to smaller oligosaccharides by the action of plasma amyicodextrin or its metabolites (for example, the decline in lases. The predominant circulating metabolites of icoserum sodium and chloride, increase in serum osmolality, dextrin are maltose (2 glucose molecules), maltotriose etc.), analytical assay interference (such as, icodextrin (3 glucose molecules), and maltotetraose (4 glucose molinterference with certain glucose assays and amylase ac- ecules), with little glucose released in the systemic circutivity assays), as well as the compatibility of icodextrin lation due to the absence of circulating maltase. The with certain drugs commonly used in peritoneal dialysis, release of glucose from the metabolized polymers occurs such as intraperitoneal insulin and antibiotics. predominantly during the intracellular metabolism of maltose or other polymers by way of cellular enzymes involved in carbohydrate metabolism. From this, it is clear METABOLIC EFFECTS OF ICODEXTRIN that the “glucose load” arising from the use of icodextrin It is important at the outset to discuss why the meta- is “functionally invisible” to the peritoneal cavity and bolic effects of a glucose polymer can be distinct from systemic circulation, and its predominant systemic expothose of glucose itself. From an overall perspective, the sure is intracellular. This metabolic profile of icodextrin net result of the use of a glucose polymer should be the provides the framework for the following discussion of same as for glucose, as a glucose polymer is metabolized the metabolic effects of icodextrin. ultimately to glucose. However, this is modulated by two