Kinetic studies of dipeptide-based and amino acid-based peritoneal dialysis solutions

Background. Dipeptide-based peritoneal dialysis solutions may have potentia l advantages compared with the glucose or amino acid-based solutions. Dipep tides may hydrolyze in the peritoneal cavity, generating constituent amino acids and thereby increasing the osmolality of the dialysate. Dipeptides ca n also be a valuable source of amino acids, which are poorly soluble in wat er, such as tyrosine. Methods. Dwell studies in rats were performed during four hours with dipept ide solutions containing five dipeptides (Gly-His, Ala-Tyr, Thr-Leu, Ser-Ph e, Val-Lys), 8, or 16 mmol/L of each dipeptide (low or high dipeptide group ). Dwell studies were also performed with a 1.1% amino acid solution (Nutri neal(R)). The model of dipeptide hydrolysis (hydrolysis rate, K-H), diffusi ve (rate constant, K-BDD) and convective transport as well as transport of constituent amino acids consisted of mass balance equations, written for ea ch dipeptide and amino acid. Results. Peritoneal volume with the amino acid solution decreased much fast er than that with the high and low dipeptide solutions. K-H for all dipepti des did not differ between the high and low dipeptide groups. In the low di peptide group, K-H was 0.004 +/- 0.004 mL/min (mean +/- SD) for Gly-His (th e lowest) and 0.088 +/- 0.048 mL/min for Thr-Leu (the highest). K-BDD was h igher than K-H for all dipeptides, the average being 0.2 +/- 0.05 mL/min. Conclusions. Dipeptides are hydrolyzed in the peritoneal cavity, generating constituent amino acids. However, the hydrolysis rate appears to be severa l times lower than the dipeptide diffusive transport rate from dialysate to blood. Due to the higher molecular weight and intraperitoneal generation o f amino acids, the dipeptide-based solutions provide more sustained ultrafi ltration than the amino acid solution. The plasma concentration of amino ac ids at 60 minutes, in relation to the dose of amino acids delivered between 0 and 60 minutes, is considerably higher during the dwells with amino acid -based solution than during dwells with the dipeptide-based solutions.