Phase II year
1988
(last award dollars: 1989)
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 revers 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.
Thesaurus Terms:Animals, Chordates, Mammals, Lagomorphs Animals, Chordates, Mammals, Rodents, Hystricomorpha, Guinea Pigs Animals, Chordates, Mammals, Rodents, Myomorpha, Mice (Laboratory) Biological Preparations And Standardization, Natural Products Produced Wit Biological Transport, Passive Transport, Osmosis Biotechnology Body Fluids, Milk Body Fluid Balance Therapy, Dialysis (Therapeutic) Body Fluid Balance Therapy, Dialysis (Therapeutic), Continuous Ambulatory Cardiovascular Function, Vasomotion Chemical Reactions, Solvolysis, Hydrolysis Enzyme Reactors Food, Dairy Products Globulins, Beta-Lactoglobulin Hexoses, Glucose Hypersensitivity Kidney Disorders, Renal Failure Kidney Disorders, Uremia Kidney Surgery, Nephrectomy Bilateral Models, Disease Models Peptides Physical Properties, Fluid State, Osmotic Pressure Physical Separation, Chromatography, High Performance Liquid Chromatograph Physical Separation, Ultrafiltration Protein Metabolism Proteins, Albumins, Lactalbumin Radioisotopes, Hydrogen Radioisotopes, Iodine Radiotracers Therapy Evaluation, Non-Human ToxicologyNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)