Peritoneal dialysis used in treating patients with end-stage renal disease utilizes the osmotic force of high concentrations of glucose to transfer water from the body pool to the dialysate as a substitute for urinary excretion. The high glucose content of the dialysate has been identified as a source of several metabolic problems in such patients, especially those who are also diabetic. In Phase I of this program we have developed a method of preparing charged peptides from milk whey protein as a substitute osmotic agent. The milk whey protein, an abundant, low cost source high in essential amino acids is digested enzymatically in a membrane reactor. A new extraction process using both dialysis and reverse osmosis permits the continuous isolation of peptides of selected molecular sizes. By virtue of their lower equivalent weight, the peptides offer the possibility of longer peritoneal persistence times (because molecular weight is higher) and equal osmotic driving force (because equivalent weights are low) compared to glucose. The feasibility of producing the desired product was shown in Phase I. Under Phase II animal studies will be determine the mass transfer rates into the circulation from peritoneal dialysate, the persistence of osmotic water transfer during dialysis, the rate of metabolism of product reaching the circulation through lymph drainage, into the circulation, and the effects of short-term chronic dialysis. In addition, acute toxicity and allergenicity tests will be performed to demonstrate the safety of the product. These studies should provide the necessary basis needed prior to clinical trials.
