title: Natural anticoagulant and fibrinolytic pathways in renal allograft failure.
abstract: This is an immunocytochemical study of the relationship between depletion of natural anticoagulant and fibrinolytic pathways and allograft survival following renal transplantation. Patients (n = 44) were classified in three groups according to the length of time between transplantation and allograft failure: group 1 (n = 14) failed within a month of transplantation; group 2 (n = 14) failed between one month and one year after transplantation; and group 3 (n = 16) failed after one year of transplantation. Control biopsies were from donor kidneys (n = 16) prior to transplantation. There were no statistically significant differences in recipient age, gender, donor kidney type (living-related versus cadaver), histocompatibility, and plasma cholesterol, triglycerides, or creatinine concentrations between groups. However, group 1 allografts had a greater depletion of the vascular heparan sulfate proteoglycan-antithrombin III natural anticoagulant pathway than allografts in group 2 or 3 (P < or = 0.05), and this depletion was associated with significantly greater fibrin deposition in group 1 than in either group 2 or 3 (P < or = 0.05). All three groups demonstrated severe depletion of tissue plasminogen activator from arteriolar smooth muscle cells and depressed fibrinolysis as evidenced by increased fibrin/plasmin ratios. However, no significant differences were found for either endothelial thrombomodulin or T cell, neutrophil, or macrophage infiltration between the groups. These data indicate that differences in graft outcome may be determined more by compromised vascular function than by the presence of cellular infiltrates.
authors.affiliation: Center for Reproduction and Transplantation Immunology, Methodist Hospital of Indiana, Indianapolis 46202.
authors.forename: R J
authors.initials: RJ
authors.lastname: Torry
authors.forename: C A
authors.initials: CA
authors.lastname: Labarrere
authors.forename: P
authors.initials: P
authors.lastname: Gargiulo
authors.forename: W P
authors.initials: WP
authors.lastname: Faulk
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology*; D000990:Antithrombin III / Q000032:analysis; D001706:Biopsy; D004730:Endothelium, Vascular / Q000737:chemistry; D005260:Female; D005337:Fibrin / Q000032:analysis; D005342:Fibrinolysis / Q000502:physiology*; D006084:Graft Rejection / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007150:Immunohistochemistry; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D013997:Time Factors
chemical_list: D000925:Anticoagulants; D000990:Antithrombin III; D005337:Fibrin