Safety and Efficacy of the Addition of Alanyl-Glutamine-Dipeptide to Dialysis Solution in Peritoneal Dialysis
Status:
Terminated
Trial end date:
2012-05-01
Target enrollment:
Participant gender:
Summary
Peritoneal dialysis (PD) is a cost effective and safe form of renal replacement therapy in
patients suffering from end stage renal disease.
However currently available PDF (peritoneal dialysis fluids) are not biocompatible for the
peritoneal cavity and its cells. Acute cytotoxic effects of the majority of the current
glucose-based PDF are caused by low pH, lactate, high glucose and its degradation products
(GDP).
Toxic effects of PDF can thus be extended to suppression of mesothelial HSR (heat shock
reactions) following PDF exposure resulting in increased susceptibility of mesothelial cells
against PDF exposure: PDF inherent stress factors fail to adequately induce HSP as effectors
of the cellular stress response - the adequate HRS rather seems to be blocked.
Hence, therapeutic approaches to activate and enhance the HSR will reduce peritoneal damage
and organ failure and improve the survival of organisms.
Preclinical results demonstrated that supplementation of PDF with pharmacological doses of
alanyl-glutamine restored HSP expression and increased the resistance of mesothelial cells in
in-vitro models of PD and preserved peritoneal integrity in in-vivo models of PD.
After these positive preclinical results, this study shall now clarify, whether the addition
of alanyl-glutamine to the most commonly used glucose-based PDF is safe and tolerable.
Therefore PDFs will be drained in a randomized cross-over study. Main outcomes measures will
be total HSP expression in peritoneal cells and changes of the peritoneal transport kinetics
and the presence/absence/severity of side effects.