Can Pentoxifylline Prevent Adverse Reactions to Hemodialysis Membranes

AbstractThe effects of pentoxifylline (PTX) on clinical and biological reactions induced by the exposure of blood to Cuprophane® were studied in comparison with a placebo (P) in patients undergoing chronic hemodialysis (HD). Six patients who had been hemodialysed for more than 3 months were enrolled in a randomised, double-blind, cross-over study. Each patient was studied during two HD sessions at an interval of 15 days, once after the administration of 800 mg/day of PTX for 3 days and once after the administration of P in the same fashion. The last administration of PTX or P took place 12 hours before the beginning of HD sessions.No adverse reaction to HD was observed after administration of PTX whereas reactions occurred in 4 patients after administration of P, consisting of both asymptomatic hypotension and vomiting in two patients, and symptomatic hypotension in two other patients. However, no significant difference was found in systolic blood pressure during HD following the two pretreatments, whereas diastolic pressure was lower after P from 30 min of HD until the end of the session.Biological status at the beginning of the HD session (i.e. 12 hours after the last intake of RTC or P) showed no differences in erythrocyte or lymphocyte counts with regard to pretreatment. In contrast, neutrophil counts were higher after PTX. Plasma levels of myeloperoxidase and lactoferrin, both markers of granulocytes lysis, were lower when patients had received PTX (10 ± 6 arbitrary units and 234 ± 123 µg/l, respectively) than following P (23 ± 14 and 390 ± 294, respectively), suggesting a protective effect of PTX in this respect. Monocyte counts were also higher after PTX. Neutrophil and monocyte adherence was similar following the two pretreatments, whereas the oxidative response of phagocytes to particulate and soluble stimuli was lower after PTX. Values for oxidant stress markers were similar whether patients had received PTX or P. Both platelet counts and platelet adherence to nylon fibers were lower after PTX.A decrease in neutrophil, monocyte and platelet counts was observed 30 min after the beginning of the HD session after patients had received P ; neutrophil and monocyte values recovered at the end of the session but platelet values remained low. The same pattern was observed for neutrophil and monocyte counts after PTX but, on the contrary, platelets counts increased by 20 % and 32 % at 30 and 240 min, respectively. Platelet adherence did not change after PTX whereas it decreased after P. Neutrophil adherence showed similar increase at 30 min of HD after both treatments and returned to normal at the end of the session. Regardless of treatment, the ex vivo oxidative response of neutrophils to various stimuli was decreased at 30 min but returned to pre-HD levels at the end of the session. Neither markers of neutrophil lysis, nor those of in vivo oxidative injury were affected by PTX. TNF plasma levels increased during HD following both pretreatments ; however, the increase was lower both at 30 and 240 min in patients who had received PTX.In conclusion, PTX would appear to have a protective effect against adverse clinical reactions to Cuprophane®. However, no relevant biological modification, with the exception of a lower increase in plasma TNF levels, was observed during HD performed after PTX. Further studies are required to confirm the favourable clinical effects of PTX and to determine the mechanisms by which they may be mediated.