Adenosine and hemodialysis in humans

Background: Infections and hypotension are serious complications that devel op during hemodialysis (HD) treatment. Adenosine (ADO), a strong hypotensiv e and immunosuppressive agent, may participate in these two HD complication s, because high concentrations of ADO metabolites are found in dialyzed hum an plasma, ADO, which is released by endothelial cells, is quickly transfor med into inosine (INO) by plasmatic ADO deaminase (ADA) and mononuclear cel l ADO deaminase (MCADA). In plasma, the degradation of ADO into INO and its uptake by red blood cells (RBC) are both very rapid, resulting in the shor t half-life of ADO in blood. Methods: Using liquid chromatography, we evaluated ADO and INO plasma conce ntrations before and after HD session. Results: Before the HD session, ADO and INO plasma concentrations were high er in hemodialyzed patients than in controls and in peritoneally dialyzed p atients. At the end of the HD session, ADO plasma concentration was increas ed. ADO plasma concentration for the undialyzed patients was in the same ra nge as that of the controls. Before IID, ADA activity was higher in hemodia lyzed patients (559+/-349 IU) than in controls (219+/-48 IU), and the activ ity rose during the session (665+/-135 IU), ADA activity in the undialyzed patients (222+/-80 TCT) was in the same range as that of the controls (219/-48 IU), Before the HD session, the MCADA activity (247+/-144 IU) was lowe r than in controls (624+/-99 Hi). HD did not modify ADO RBC uptake. ADO inh ibited mononuclear cell proliferation and interferon-gamma production in hu mans, Finally, as much as 50 muM INO does not inhibit ADO uptake by RBC and does not modify ADA and MCADA activities. Conclusions: These data indicate that chronic HD inhibited MCADA activity a nd increased ADO plasma concentration. Both high ADO plasma concentration a nd low MCADA activity may be involved in dialysis induced immune system fai lure and thereby favor infectious diseases.