Myeloperoxidase up-regulation during haemodialysis: is heparin the missing link?

Myeloperoxidase up-regulation during haemodialysis: is heparin the missing link? Sir, We read with interest the recent series of articles showing a striking increase in blood myeloperoxidase (MPO) levels during haemodialysis (HD) sessions [1–3]. In this setting, the enzyme is traditionally regarded as a marker of neutrophil degranulation and thus, of dialyser membrane biocompat-ibility, as well as generation of oxidative stress [1–5]. Some results of the above studies and their interpretations seem, however, not to be corroborated enough and indicate the existence of other unrecognized factors responsible for MPO up-regulation during HD [1,2]. For example, in the study by Wu et al. [1] the increase in plasma MPO was as much as 3-fold vs baseline with a biocompatible polysulfone membrane, occurring as early as 15 min from the start of HD and, surprisingly, was not accompanied by a fall in circulating neutrophil counts. In the study by Gritters et al. [2] serum MPO levels almost doubled after the first passage of blood through the high-flux polysulfone dialyser. Notably, the effect was only observed when either unfractionated heparin or low-molecular-weight heparin dalteparin was used for temporary HD anticoagulation, and then disappeared with regional trisodium citrate anticoagulation [2]. The authors ascribed the latter absence of MPO release to the calcium-free environment created within the dialyser, and suggested that it could be a valuable approach to avoid overdialytic neutrophil degranulation. They seem, however, to have overlooked the previous report indicating no MPO up-regulation during HD treatments anticoagulated with nafamostate mesylate instead of heparin [4]. In the most recent trial, Krieter et al. [3] showed a remarkable, 6-fold rise in blood MPO levels taking place 5 min after the start of HD. They also revealed a small ($9%) but significant difference between MPO levels in blood leaving vs entering the filter, which confirms the actual but negligible intra-dialyser neutrophil degranulation. On the basis of the early high MPO levels in the pre-dialyser blood, the authors attentively concluded that the contact of blood with the filter membrane could not be the only cause of MPO generation [3]. Unfortunately, both Wu et al. [1,5] and Krieter et al. [3] failed to specify the anticoagulation strategy used in their HD patients, ascribed the very early MPO upregulation to either 'the dialysis per se and dialysate contaminants' [5] or 'shear forces through the blood pump' [3] and prematurely ended with the statement that MPO is a useful and reliable …