Interleukin-1 receptor antagonist synthesis by peripheral blood mononuclear cells: A novel predictor of morbidity among hemodialysis patients

Proinflammatory cytokines have been implicated in the short- and long-term morbidity experienced by hemodialysis (HD) patients. The present study, whi ch is based on long-term follow-up of a cohort of 37 patients, relates peri pheral blood mononuclear cell (PBMC) interleukin-1 receptor antagonist (IL- 1Ra) synthesis (a reliable marker of IL-1 beta synthesis in HD patients) an d plasma levels of an acute phase reactant, lipopolysaccharide binding prot ein (LBP), to clinical outcomes. In July 1993, predialysis blood samples fr om these patients were collected and IL-1Ra synthesis by PBMC and plasma LB P was measured. Hospital records were reviewed and patient follow-up data w ere obtained until December 1997 (54 mo) or death, whichever occurred earli er. The effect of age, diabetes, endotoxm- and IgG-stimulated IL-1Ra synthe sis, and plasma LBP levels on mortality was assessed using the Cox proporti onal hazard regression model. Poisson regression was used to determine pote ntial relationships between the number of outcome events and each continuou s risk factor. Twenty-two patients (59%) died during the follow-up period. Mortality was unrelated to IL-1Ra synthesis but did increase with age (rela tive risk, 1.05/yr; P = 0.01) and diabetes (relative risk, 3.00/yr; P = 0.0 3). Cardiovascular event rates were higher among older individuals and in t hose with higher endotoxin-stimulated PBMC IL-1Ra synthesis. Cardiovascular events increased with plasma LBP levels in the range of 9,000 to 12,000 pg /ml but then seemed to decrease. In contrast, older age and low IgG-stimula ted IL-1Ra synthesis were associated with an increased risk of infectious e vents. The results of this study demonstrate an interesting link between st imulus-dependent variability in IL-1Ra synthesis by PBMC and clinical outco mes among patients on chronic HD and provide interesting targets for therap eutic interventions in this vulnerable patient population.