The accumulation of urea is one of the many consequences of renal failure. Urea is not regarded as a highly toxic substance in man. However urea forms significant amounts of cyanate spontaneously in solution. Cyanate forms carbamoylated compounds with Alpha amino, Epsilon amino, sulfhydryl or hydroxyl moieties of amino acids, peptide and proteins. The proposed study is based upon the hypothesis that these endogenously carbamoylated molecules found in the patients with end stage renal disease (ESRD) are foreign to the organism and may have decreased function and/or be immunogenic because of their change in structure. The working hypothesis is that decreased carbamoylation of amino acids, peptides or proteins or the continuous removal of urea, cyanate and carbamoylated molecules has a role in the clinical improvement in anemia and other parameters in patients with ESRD treated by continuous ambulatory peritoneal dialysis (CAPD). A uremic toxin must be chemically identifiable in the biological fluids of uremic patients in a measurable concentration and be in higher concentration in ESRD than in normal individuals. High concentrations of the toxin must correlate with uremic symptoms. The immediate aim of this study is 1.) To establish a rapid and sensitive measurement for carbamoyl amino acids using HPLC. The HPLC method will be used to study a.) the degree of carbamoylation of amino acids, peptides and proteins; b.) to quantitate free carbamoyl amino acids in plasma and in dialysate in the same time frame; to establish a ratio of normal to modified amino acids and correlate these with specific uremic symptoms; 2.) To measure the antigenicity of the carbamoylated molecules by testing the plasma of patients with ESRD for circulating antibodies to carbamoylated moieties; 3.) With the new method to quantitate carbamoyl amino acids and the degree of carbamoylation of a protein, to explore model systems that would effectively remove urea and cyanate using CAPD. In the long term to further elucidate the role of the carbamoylated molecules in the clinical differences found in patients with ESRD treated by CAPD and to utilize knowledge from this study to develop more efficient and less costly modes of ESRD therapy.
| Kraus, L M; Jones, M R; Kraus Jr, A P (1998) Essential carbamoyl-amino acids formed in vivo in patients with end-stage renal disease managed by continuous ambulatory peritoneal dialysis: isolation, identification, and quantitation. J Lab Clin Med 131:425-31 |
| Kraus, L M; Elberger, A J; Handorf, C R et al. (1994) Urea-derived cyanate forms epsilon-amino-carbamoyl-lysine (homocitrulline) in leukocyte proteins in patients with end-stage renal disease on peritoneal dialysis. J Lab Clin Med 123:882-91 |
| Kraus, L M; Miyamura, S; Pecha, B R et al. (1991) Carbamoylation of hemoglobin in uremic patients determined by antibody specific for homocitrulline (carbamoylated epsilon-N-lysine). Mol Immunol 28:459-63 |
| Kraus, L M; Kraus Jr, A P (1991) Tyrosine and N-carbamoyl-tyrosine in end-stage renal disease during continuous ambulatory peritoneal dialysis. J Lab Clin Med 118:555-62 |
