Metabolic factors and outcome of organ transplantation.
Chronic vascular rejection (CVR)--transplant atherosclerosis--is a major problem in organ transplantation and a leading cause of late graft failure. The purpose of the present investigation was to examine the impact of metabolic factors on the outcome of experimental and clinical transplantation. In an experimental model of CVR in rat cardiac allografts it was shown that the development of proliferative vascular lesions, characteristic of CVR, was accelerated 2-4 times by a cholesterol enriched diet. Renal transplant patients with manifest CVR had hyperlipoproteinaemia and atherogenic lipid patterns, the degree of which correlated with the histopathological severity of CVR and was only partially explained by renal dysfunction. The influence of pre-existing lipoprotein abnormalities on graft function was investigated prospectively in renal transplant recipients. It was found that patients with pretransplant hypercholesterolaemia had an increased number of acute rejection episodes, worse graft function and a higher degree of vascular intimal hyperplasia at six months posttransplantation and more graft losses during follow-up. Oxidatively modified LDL may be the link between hypercholesterolaemia and graft failure. Plasminogen activator inhibitor type-1 (PAI-1), a major inhibitor of fibrinolysis and another risk factor for atherothrombosis, which is associated with features of the metabolic risk factor syndrome (Syndrome X) was also followed prospectively. Patients presenting with all features of this syndrome six months after transplantation were at increased risk of losing their graft during a three-year follow-up. Pretransplant hypercholesterolaemia was associated with a more than a two-fold increase in the risk of graft failure during the first two posttransplant years, and elevated PAI-1 levels before transplantation with a five-fold increase during the first three years. A chronic graft damage (CGD) score was constructed for glomerular, vascular and tubulointerstitial changes characteristic of CVR. The CGD score at six months was higher in patients with hypercholesterolaemia or elevated PAI-1 activity before transplantation. An elevated CGD score at six months predicted an eight-fold increase in the risk of renal allograft failure within three years following transplantation. It can be anticipated that intervention directed against lipid abnormalities or other metabolic risk factors may improve the long-term success rate in organ transplantation.
Dimény
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Department of Internal Medicine, University Hospital, Uppsala, Sweden.
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology* / Q000378:metabolism; D005260:Female; D006084:Graft Rejection / Q000378:metabolism / Q000473:pathology; D016027:Heart Transplantation / Q000473:pathology*; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications; D016030:Kidney Transplantation / Q000473:pathology*; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D051381:Rats; D011919:Rats, Inbred Strains
D008074:Lipoproteins