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New Osmotic Agents for Peritoneal Dialysis: Where We Are and Where We're Going

The practice of pertoneal dialysis has changed dramatically since the introduction of continuous ambulatory peritoneal dialysis (CAPD) more than a decade ago. It is now an established alternative to hemodialysis in managing patients with end stage renal failure. The technique is practiced worldwide in more than 50 countries and is utilized in 13% of the world’s dialysis population ( 1). Despite this fundamental change, the basic principle used to generate osmotic forces across the peritoneum has remained unaltered. This principle is based on the traditional concept that osmotic flow across a semi-permeable membrane occurs only along the osmolality gradient, from solution of low to high osmolality, and therefore always necessitates the use of solutions relatively hyperosmotic to plasma. Since low molecular weight solutes (“crystalloid”) generate greater osmolality per unit mass, these substances have been regarded as the most effective osmotic agents. Among the many small molecular weight osmotic agents evaluated (2), only glucose proved to be safe as well as effective, which led to its widespread use (3). However, due to the permeable nature of the peritoneal membrane, it was soon realized that the osmotic force across it was generally below that value derived from the theoretical laws of osmosis. This less than “ideal” semi-permeable membrane, allowing rapid absorption of glucose with equally rapid dissipation of the osmolality gradient, produced ultrafiltration (UF) of short duration (4). While this was of little significance during short dwell (30-60 min) intermittent peritoneal dialysis (IPD), in CAPD (where exchanges last for 4-8 hours) reabsorption of initially ultrafiltered peritoneal fluid occurs especially during the long overnight exchanges. In addition, the continuous daily absorption of glucose from dialysate ( 150-300 gm/day) aggravates such longterm metabolic complications as hyperglycemia, hyperinsulinemia, hyperlipidemia and obesity (5 ) . Recently there has also been a growing concern regarding the unphysiological nature of this dialysis solution, particularly its hyperosmolality and low pH, which may damage the peritoneum and, therefore possibly threaten the very survival of the technique (6, 7).