グアニジン誘導体の臨床的研究 --慢性腎不全の長期透析例について--

Abstract

The serum level of guanidine compounds was determined in the patients under maintenance hemodialysis for 1/2 to 5 years. The improved Yatzidis' method as well as column chromatography was adopted for the determination. The serum concentration of the guanidine compounds was obviously high before dialysis. Out of Sakaguchi reaction positive substances, guanidinoacetic acid (GAA) and guanidinosuccinie acid (GSA) were abundantly detected, whereas arginine and methylguanidine (MG) were almost same as the normal control subjects. Because MG has been thought to be one of the important factors causing uremic symptoms, this result was unexpected. Pre-dialysis level of guanidine bases showed significant correlation with that of BUN, uric acid and creatinine, the best correlation being with creatinine. GSA or GAA level showed no correlation with the levels of these three substances. In the long term dialysis cases, the blood level of GAA was proved to be higher than GSA. After 8 hours hemodialysis with Kiil dialyzer, GAA and GSA level remarkably diminished but arginine did not change. Thus, GAA and GSA were proved to be dialysable substances. Hemorrhagic tendency is known to be one of the important uremic symptoms. In order to investigate the relationship between guanidine compounds and uremic bleeding, the platelet factor 3 availability (PF 3a) in vivo was evaluated by means of the ADP-Stypven time. The ADP-Stypven time was found to be correlated well with GSA (r=0.86) and GAA (r=0.66). The ADP platelet aggregation was inhibited by high guanidine compounds level. In vitro study also proved inhibitory action of all of GSA, GAA, MG, urea and creatinine on the ADP-8typven time as well as on the ADP-aggregation. Hemolytic index, which is known to be often accelerated in the patients under the maintenance hemodialysis, correlated well with the serum guanidine level (GSA: r=0.92, GAA: r=0.79). The life span of 5lCr-labeled erythrocytes was shortened by the high level of GSA and GAA probably through hemolytic action. The serum level of vitamin E was determined before and after hemodialysis because this vitamin is known to be antihemolytic. The serum level of vitamin E did not change by hemodialysis but was approximately 50 % of the normal control level. As the hemolytic index diminished after hemodialysis, uremic toxins, but not vitamin E, seemed to be closely related with uremic bleeding.