Carbohydrate-based peritoneal dialysis fluid comprising glutamine residue

Abstract

The present invention relates to a carbohydrate-based peritoneal dialysis fluid, containing a compound selected from the group consisting of glutamine, preferably L-glutamine; a dipeptide capable of releasing glutamine, L-glutamine in free form, preferably selected from the group consisting of glutaminyl-glycine, glycinyl-glutamine, glutaminyl-alanine, alanyl-glutamine; an oligopeptide consisting of two to seven glutamine, preferably L-glutamine residues; and mixtures thereof. The peritoneal dialysis fluids of the present invention are useful for inhibition of technical failure in a person undergoing peritoneal dialysis treatment.

Description

[0001]This application is a Continuation of co-pending U.S. patent application Ser. No. 14 / 081,835, filed on Nov. 15, 2013, which is a Continuation of U.S. patent application Ser. No. 12 / 529,537 filed on Sep. 1, 2009 (now abandoned), which is the National Phase of PCT International Application No. PCT / AT2008 / 000072 filed on Mar. 3, 2008, which claims priority under 35 U.S.C. 119(a) to Austrian Patent Application No. A 340 / 2007 filed on Mar. 2, 2007, all of which are hereby expressly incorporated by reference into the present application.[0002]The present invention relates to a peritoneal dialysis fluid (in the following also referred to as “PDF”).[0003]Peritoneal dialysis fluids remove solutes and water from the uremic patient. Several clinical and experimental observations have shown that PDF is cytotoxic, associated with a risk of technical failure of up to 30% with long term peritoneal dialysis (PD) treatment (6). Therefore, prolonged PD treatment frequently results in severe chr...

AI Technical Summary

Benefits of technology

[0004]Current research therefore aims to increase biocompatibility of PDF and thereby reduce mesothelial cell damage during PD. New and improved formulations have indeed shown to be less toxic in several in-vitro and in-vivo, experimental and clinical studies (7, 10). Addition of the antioxidant / scavenger Carnosine (a β-alanyl-L-histidine dipeptide), or Glutathion (gamma-glutamyl-L-cysteinyl-glycine) and related compounds (such as the cysteine prodrug L-2-oxothiazolidine-4-carboxylate) were shown to have a positive influence on PDF biocompatibility and to passively reduce the deleterious impact of glucose degradation products in PD (20-22).

[0008]Overexpression of HSP resulted in survival of an usually lethal PDF exposure in the in-vitro model of PD and prevented mesothelial cells from detachment from their peritoneal lining in the in-vivo model of PD (5, 9).

[0010]It is an object of the present invention to provide a carbohydrate-based peritoneal dialysis fluid which has less cytotoxicity than previously known products. Especially, it is an object of the present invention to provide a carbohydrate-based peritoneal dialysis fluid which inhibits technical failure in a patient undergoing a PD-treatment by actively optimizing cellular responses to pathophysiological stress upon PDF exposure.

Problems solved by technology

Therefore, prolonged PD treatment frequently results in severe chronic damage to the integrity of the peritoneal membrane.

PDF exposure impairs peritoneal cell metabolism, reduces proliferation and increases cell death, as well as disrupts cytoskeletal organization and cell signaling, including the regulation of differentiation and inflammation.

Analysis of sequential peritoneal biopsy specimens from patients undergoing PD revealed deleterious structural alterations.

These morphological changes result in severe disruption of the barrier function of the peritoneum as a semi-permeable dialysis membrane.

However, the main working principle of PDF is removal of solutes and water from the uremic patient due to its hypertonicity.

However, none of the used protocols to induce overexpression of HSP—such as hyperthermia or transient transfection—are attractive approaches in the clinical setting of PD.

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