ROLES OF RENAL CATABOLISM AND UREMIA IN MODIFYING CLEARANCE OF FIBRINOGEN AND ITS DEGRADATIVE FRAGMENTS D AND E

  • 1 January 1976
    • journal article
    • research article
    • Vol. 87  (6) , 934-946
Abstract
Elevated levels of fibrinogen/fibrin degradation products (FDP) occur in uremia, and are possibly in part related to i.v. coagulation in the kidney. Delayed catabolism of fibrinogen fragment D may occur in anephric animals. To further evaluate FDP catabolism in the kidney, turnover studies of purified dog 131I-Fg-D (iodine-131 fragment D) and 125I-Fg-E were performed on dogs before and after acute subtotal nephrectomies, and later during chronic uremia. 131I-fibrinogen clearances were also performed. Slowed catabolism of Fg-D and Fg-E was observed in both the acute and chronic uremic stages. Altered urinary excretion was not a factor as only minimal amounts of Fg-D and Fg-E were excreted in the urine of the control animals. In the 131I-fibrinogen studies, there were significant changes in plasma volume, fibrinogen t1/2, and intravascular/extravascular distribution, but not in fractional catabolic rate. To fully differentiate the effects of uremia from those of loss of catabolic renal tissue, the Fg-D and Fg-E turnover studies were repeated on other animals with intact kidneys whose ureters were diverted into the peritoneum and compared to subsequent studies after total nephrectomy. The control and ureter-severed studies had same clearance pattern, whereas decreased catabolism occurred in the nephrectomized dogs. The results demonstrate uremia per se does not have a major effect upon the catabolism of fibrinogen, Fg-D, and Fg-E. Loss of renal tissue does impair the clearance of Fg-D and Fg-E, indicating these proteins are normally catabolized in part by the kidneys. Thus elevated plasma FRA (fibrinogen-related antigen) in uremic patients may reflect decreased Fg-D and Fg-E catabolism rather than increased FD production from primary or secondary fibrinolysis.