title: L-carnitine is an osmotic agent suitable for peritoneal dialysis.
abstract: Excessive intraperitoneal absorption of glucose during peritoneal dialysis has both local cytotoxic and systemic metabolic effects. Here we evaluate peritoneal dialysis solutions containing L-carnitine, an osmotically active compound that induces fluid flow across the peritoneum. In rats, L-carnitine in the peritoneal cavity had a dose-dependent osmotic effect similar to glucose. Analogous ultrafiltration and small solute transport characteristics were found for dialysates containing 3.86% glucose, equimolar L-carnitine, or combinations of both osmotic agents in mice. About half of the ultrafiltration generated by L-carnitine reflected facilitated water transport by aquaporin-1 (AQP1) water channels of endothelial cells. Nocturnal exchanges with 1.5% glucose and 0.25% L-carnitine in four patients receiving continuous ambulatory peritoneal dialysis were well tolerated and associated with higher net ultrafiltration than that achieved with 2.5% glucose solutions, despite the lower osmolarity of the carnitine-containing solution. Addition of L-carnitine to endothelial cells in culture increased the expression of AQP1, significantly improved viability, and prevented glucose-induced apoptosis. In a standard toxicity test, the addition of L-carnitine to peritoneal dialysis solution improved the viability of L929 fibroblasts. Thus, our studies support the use of L-carnitine as an alternative osmotic agent in peritoneal dialysis.
authors.affiliation: Department of Medicine, Institute of Nephrology, University G. d'Annunzio, Chieti-Pescara, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Bonomini
authors.forename: Assunta
authors.initials: A
authors.lastname: Pandolfi
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Di Liberato
authors.forename: Sara
authors.initials: S
authors.lastname: Di Silvestre
authors.forename: Yvette
authors.initials: Y
authors.lastname: Cnops
authors.forename: Pamela
authors.initials: P
authors.lastname: Di Tomo
authors.forename: Mario
authors.initials: M
authors.lastname: D'Arezzo
authors.forename: Maria P
authors.initials: MP
authors.lastname: Monaco
authors.forename: Annalisa
authors.initials: A
authors.lastname: Giardinelli
authors.forename: Natalia
authors.initials: N
authors.lastname: Di Pietro
authors.forename: Olivier
authors.initials: O
authors.lastname: Devuyst
authors.forename: Arduino
authors.initials: A
authors.lastname: Arduini
mesh_terms: D000818:Animals; D051398:Aquaporin 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D002331:Carnitine / Q000493:pharmacokinetics / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015314:Dialysis Solutions / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009995:Osmosis / Q000187:drug effects; D010530:Peritoneal Dialysis / Q000379:methods*; D010537:Peritoneum / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014462:Ultrafiltration / Q000379:methods
chemical_list: C496020:AQP1 protein, human; C496021:Aqp1 protein, mouse; D015314:Dialysis Solutions; D051398:Aquaporin 1; D005947:Glucose; D002331:Carnitine