High adenosine and deoxyadenosine concentrations in mononuclear cells of hemodialyzed patients

Infections are one of the most important complications of hemodialysis (HD) . The high concentrations of adenosine (Ado) and of its metabolites during HD may contribute to the dialysis-induced immune deficiency through their k nown ability to alter lymphocyte function. The influence of HD on Ado metab olism was assessed in mononuclear cells through the measurement of (1) the concentrations of nucleosides in mononuclear cells and (2) the activities o f mononuclear cell Ado deaminase (MCADA) and Ado kinase, two enzymes involv ed in Ado concentration regulation. Nine end-stage renal failure hemodialyz ed patients (five men and four women; mean age, 69 +/- 10 yr) and eight hea lthy volunteers (four men and four women; mean age, 53 +/- 19 yr) were incl uded in the study. Before HD, Ado, deoxyadenosine, and inosine concentratio ns were respectively 2.9-, 2.5-, and 2.5-fold higher in mononuclear cells o f patients than in healthy volunteers. During KD, Ado concentration decreas ed by 34%, whereas inosine concentration increased by 27%. Before HD, MCADA activity level was 2.1-fold lower in patients than in control subjects. Af ter HD, MCADA activity increased by nearly 50% but remained lower than in c ontrol subjects. Ado kinase activity level of patients did not differ from that of control subjects and was unchanged by HD. The influence of Ado on i n vitro mononuclear cell proliferation and interferon-gamma production also was evaluated. Ado inhibited cell proliferation and interferon-gamma produ ction in a dose-dependent manner, and these inhibitions were stronger for p atients than for healthy volunteers. The high concentrations of Ado and deo xyadenosine in mononuclear cells and the low MCADA activity level likely ar e involved in the immune defect of patients who are undergoing HD.