NATURAL ANTICOAGULANT AND FIBRINOLYTIC PATHWAYS IN RENAL-ALLOGRAFT FAILURE

This is an immunocytochemical study of the relationship between deplet ion of natural anticoagulant and fibrinolytic pathways and allograft s urvival following renal transplantation. Patients (n=44) were classifi ed in three groups according to the length of time between transplanta tion and allograft failure: group 1 (n=14) failed within a month of tr ansplantation; group 2 (n=14) failed between one month and one year af ter transplantation; and group 3 (n=16) failed after one year of trans plantation. Control biopsies were from donor kidneys (n=16) prior to t ransplantation. There were no statistically significant differences in recipient age, gender, donor kidney type (living-related versus cadav er), histocompatibility, and plasma cholesterol, triglycerides, or cre atinine concentrations between groups. However, group 1 allografts had a greater depletion of the vascular heparan sulfate proteoglycan-anti thrombin III natural anticoagulant pathway than allografts in group 2 or 3 (P less than or equal to 0.05), and this depletion was associated with significantly greater fibrin deposition in group 1 than in eithe r group 2 or 3 (P less than or equal to 0.05). All three groups demons trated severe depletion of tissue plasminogen activator from arteriola r smooth muscle cells and depressed fibrinolysis as evidenced by incre ased fibrin/plasmin ratios. However, no significant differences were f ound for either endothelial thrombomodulin or T cell, neutrophil, or m acrophage infiltration between the groups. These data indicate that di fferences in graft outcome may be determined more by compromised vascu lar function than by the presence of cellular infiltrates.