Hemodialysis with Polymethylmethacrylate Restores the Response to Hepatitis B Vaccination in Chronic Dialysis Patients: Hypothesized Mechanism of Action

Abstract

Patients undergoing hemodialysis often present with a reduced response to anti-hepatitis B virus (anti-HBV) vaccination. The soluble form of CD40 (sCD40) is elevated in hemodialysis patients and this has been shown to correlate with lack of response to anti-HBV vaccination. Due to its high molecular weight, conventional dialyzers cannot clear sCD40. Previous studies have demonstrated, that dialysis membranes in polymethylmethacrylate (PMMA) can reduce the levels of sCD40. We have studied the effect of dialysis with PMMA membranes in patients who were non-responders to anti-HBV vaccination after a complete cycle of vaccinations. Interestingly, we found that significantly more patients in the PMMA group were able to mount a response to vaccination, compared to the control group (P = 0.04). Materials and Methods PatientsPatients were included in this study if they had been on maintenance thrice-weekly dialysis treatment and had undergone at least one complete cycle of anti-hepatitis B virus vaccination (20 mg Fendrix, administered at 0, 1, 2 and 6 months) and were non-responders (e.g. anti-HBV antibody titre <10 UI/L). Patients were excluded from this study if they had undergone dialysis treatment with PMMA dialyzers prior to enrolment and/or if they had active neoplasia. All patients gave their informed consent to participate in the study. Following enrolment, patients were randomized into two groups, a control group that continued on the same dialysis treatment as previously, and a treatment group that was shifted to dialysis with PMMA series BK-F (1.3 to 2.1 m 2 ). The treatment with PMMA continued until after the administration of the fourth vaccination. Patients underwent thrice-weekly dialysis for three months and were then administered the fourth vaccination dose. Immune response was evaluated hereafter. Laboratory parametersSerum levels of sCD40 were measured every four weeks by enzyme-linked immunosorbent assay (ELISA) during the 12 weeks of study and again 4 weeks after anti-hepatitis B virus vaccination. ELISA was performed essentially as described by Contin et al.[2], all samples were measured in duplicates and the mean concentration was calculated. Blood urea nitrogen (BUN) concentrations, Kt/V and C-reactive protein (CRP) were evaluated every four weeks.

Examination of the Effect of Switching Dialysis Membranes on the Immune Response to Influenza Virus Vaccination in Hemodialysis Patients

“…Regarding changing the modality, Nongnuch and coworkers reported that seroconversion rates for influenza vaccine were not significantly different between HD and HDF therapies, although seroprotection in patients treated with HDF was sustained for longer compared with those treated by HD [ 21 ]. Regarding the change in dialysis membranes, some studies have reported that the use of PMMA dialyzers has the potential to improve the response to vaccine against HBV in HD patients who were treated with PS-type dialyzers and were classified as nonresponders to the vaccine [ 11 , 12 , 16 ]. These reports showed the removal of soluble CD40 sCD40, which can suppress the interaction between T and B cells, as the possible mechanism involved.…”

“…Regarding the improvement in the immune response, it was reported that the response to vaccine against hepatitis B virus could be improved in HD patients who were classed as nonresponders previously, when the dialyzer was changed to BK-F, a dialyzer that uses PMMA membrane [ 11 , 12 ]. Furthermore, it was shown that removal of soluble CD40 (sCD40), which plays a role in antibody production and was not removed by the dialyzer using PS membrane, may be related to this improvement [ 11 , 12 , 16 ].…”