Upregulation of Myeloperoxidase in End Stage Renal Disease and Its Modulation by Hemodialysis. A Paradoxical Paradigm.

Myeloperoxidase (MPO), a heme protein released from activated leucocytes mediates the generation of reactive intermediates promoting lipid peroxidation. MPO is secreted by activated neutrophils, monocytes and macrophages. MPO has been reported to be a marker of hemodialysis procedure biocompatibility and oxidative stress with discordant results. Different dialyzer membranes and the type of anticoagulation used contribute to the regulation of MPO in end stage renal disease (ESRD) patients. To validate the hypothesis that MPO is upregulated in ESRD and hemodialysis differentially modulates the MPO in patients with this syndrome, blood plasma samples from 70 patients on maintenance hemodialysis prior to and after hemodialysis session. The pre-dialysis levels of MPO antigen as measured by an ELISA method (Assay Design, ) ranged from 0.5–125 ng/ml (31.1±28.6 ng/ml), in contrast to the aged match normal controls where the range was 0.21–7.5 ng/ml, (2.8±1.3 ng/ml). After dialysis, 10/70 patients did not show any changes in the MPO level, whereas, 4 patients showed a decrease, the remaining 56 patients exhibited marked increase in the circulating MPO level ranging from 9.5–201 ng/ml (74.4±48.2 ng/ml). Progressive atherosclerotic changes are associated with the severity of ESRD where oxidative stress is known to play a major role. While MPO may mediated oxidative stress the beneficial consequences include its depletion from the vascular site. Hemodialysis in ESRD generally results in a downregulation of inflammatory mediators. The increased MPO level in ESRD represents a paradoxical and complex process which may contribute to the pathogenesis of ESRD. The role of different anticoagulants and dialyzer membrane and other factors in regulating circulating MPO level may be important in elucidating the pathogenesis and outcome of this syndrome.