title: Plasminogen activator inhibitor-1 activity in chronic renal disease and dialysis.
abstract: The activity of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis, is associated with insulin resistance (IR) and the risk of venous and arterial thrombotic cardiovascular disease (CVD) in the general population, and may behave as an acute-phase reactant. PAI-1 activity was measured in 124 patients with chronic renal disease, and its relationship with alterations in metabolic, lipid, and cytokine parameters and the prevalence of CVD complications was explored. Patients with chronic renal disease not requiring dialysis were divided into a low proteinuric ([LP]n = 30) or high proteinuric ([HP]n = 31) group and compared with patients on continuous ambulatory peritoneal dialysis ([CAPD]n = 32) or hemodialysis([HD]n = 31) and with 31 healthy controls. Patients on HD had significantly lower PAI-1 activity than HP, CAPD, and control groups, but no group had significantly higher values than the controls (AU/mL: 7.4 +/- 3.8 HD, 11.2 +/- 8.4 CAPD, 9.4 +/- 5.4 LP, 12.1 +/- 8.0 HP, 11.4 +/- 6.6 controls, P = .04). Interleukin-6 (IL-6), the mediator of the acute-phase response, was determined in a subset of patients and was significantly increased in HD, CAPD, and LP groups compared with the controls (median, pg/mL: 4.6 HD, 4.0 CAPD, 2.9 LP, 2.4 HP, and 1.5 controls, P < .001), but did not correlate with PAI-1. PAI-1 independently correlated with body mass index (BMI), triglycerides, and lipoprotein(a) [Lp(a)] in stepwise regression for all patients. Dividing the whole patient group by tertiles of triglycerides and BMI, increased PAI-1 was confined to the subgroup of patients with both obesity (BMI > 26.7 kg/m2) and hypertriglyceridemia (triglycerides > 2.5 mmol/L). These data suggest that PAI-1 activity in chronic renal disease and dialysis was more strongly associated with the common metabolic abnormalities of obesity and hypertriglyceridemia than with renal disease status, dialysis, or a chronic inflammatory state. This study does not support but does not exclude a major role for increased PAI-1 activity in CVD risk in chronic renal disease.
authors.affiliation: Oxford Renal Unit, The Churchill Hospital, Headington, United Kingdom.
authors.forename: A B
authors.initials: AB
authors.lastname: Irish
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000502:physiology; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000503:physiopathology; D017270:Lipoprotein(a) / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000503:physiopathology; D010531:Peritoneal Dialysis, Continuous Ambulatory; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood* / Q000502:physiology; D006435:Renal Dialysis; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D015850:Interleukin-6; D017270:Lipoprotein(a); D017395:Plasminogen Activator Inhibitor 1; D014280:Triglycerides