Kinetic analysis of transport and hydrolysis of dipeptides, a new osmotic agent for peritoneal dialysis solution

A mixture of dipeptides (DP) have been proposed as an alternative (to glucose and amino acids, AA) osmotic agent in peritoneal dialysis (PD) solutions. The following solutions were used: (1) the amino acids (AA) solution containing leucine, valine, lysine, isoleucine, threonine, phenylalanine and histidine (tyrosine was omitted because of its poor solubility), (2) the dipeptide (DP) solution containing leucyl-valine, lysyl-isoleucine, threonyl-phenylalanine and histidyl-tyrosine. Sixteen Sprague-Dawley rats were used in the experiments. Kinetic models were developed for estimation of the diffusive mass transport coefficient between the peritoneal cavity and blood (KBD), the DP hydrolysis rate coefficient (KH ) and the AA clearance in the body (KC). The calculations show that KH is about ten times smaller than KBD. Thus, the hydrolysis rate in the peritoneal cavity is much smaller than the diffusive transport rate of DP. KBD for AA appeared to be similar to KBD for dipeptides. KC was much higher than KBD for AA. This finding explains the rapid clearance of amino acids from blood. The peritoneal transport characteristics of AA and DP were similar; however, their kinetics in blood considerably differed. The DP solution resulted in a less pronounced increase of the AA concentrations in blood, suggesting that the DP solution could provide the AA supply/delivery in a more physiological way.