NDT Advance Access originally published online on February 7, 2006
Nephrology Dialysis Transplantation 2006 21(4):1128-1129; doi:10.1093/ndt/gfl004
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Reply
Email: mareillegritters{at}hotmail.comSir,
We would like to thank the authors for their comments on our study. In their letter, they suggest that the haemodialysis (HD)-induced rise in myeloperoxidase (MPO) results from mobilization from the endothelium by exogenous-administered heparin. However, as described in our recent [1] and earlier studies [2,3], MPO reached its peak levels directly after first passage (t1 min). Moreover, substantial blood cell degranulation was observed in a closed loop recirculation model [4]. This process could be blunted by the chelation of plasmatic calcium (Ca) by sodium citrate or EDTA, and did not correlate with C3a or C5a concentrations [5]. The latter finding is in agreement with clinical studies, showing that degranulation and complement activation depend to a large extent on the type of dialyser used and are, in fact, independent of each other [6]. Based on the above mentioned data from clinical and experimental studies, it seems justified to conclude that MPO release occurs with certainty within the ECC, whereas endothelial mobilization remains to be proven. With respect to the cause of HD-induced degranulation, the mode of anticoagulation appears to be crucial. Several studies have indicated that Ca plays a critical role in the interaction between platelets and leukocytes [7]. As not only aggregation of platelets, but also aggregation between platelets and leukocytes is an active process [8], it is to be expected that these phenomena are abolished in a Ca free environment, as created by citrate. With respect to heparin, it was recently shown in vitro that this substance binds to MPO and inhibits its binding to the endothelium [9]. Moreover, heparin might compete with MPO for binding onto the surface of dialyser membranes, or vice versa, the absence of heparin might facilitate its binding to these materials. Therefore, in a previous study [10], dialysers were pre-rinsed with heparin, both before the administration of citrate and low-molecular-weight heparin (LMWH). From this study, it appeared that pre-rinsing had no effect on the MPO concentrations in the efferent line. In an additional experiment [1], we studied the influence of LMWH on the release of the platelet degranulation product PF4. Dalteparin (4000 IU) was given 10 min before the start of HD (t0). PF4 concentrations were measured at t–10 (before injection), t0 (before start HD), t5, t30, t60 and t150 min. Anti-Xa activity was measured to confirm the systemic activity of dalteparin. As can be seen from Table 1, the PF4 concentration increased less than 2-fold from t–10 to t0, despite evident systemic activity of dalteparin at t0, whereas shortly after the start of HD a more than 15-fold increase was seen. Therefore, the rise at t5 resulted most likely from the degranulation of platelets and not from LMWH-induced endothelial release.
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Finally, it should be mentioned that heparin indeed can mobilize MPO from the endothelium in vitro, as was shown by Daphna et al. [11] in a model using calf aortas.
Conflict of interest statement. None declared.
1 Department of Nephrology2 Department of Clinical Chemistry, Medical Center Alkmaar, Alkmaar3 Department of Nephrology4 Department of Clinical Chemistry5 Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands
References
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