Post-dilution haemodiafiltration and low-flux haemodialysis have dissimilar effects on platelets: a side study of CONTRAST.
BACKGROUND
Cardiovascular disease (CVD) is the leading cause of death in patients with end-stage renal disease (ESRD). Platelet (PLT) dysfunction, which is a well-known phenomenon in advanced chronic renal failure, corresponds positively with CVD in these patients. The accumulation of retained uraemic toxins might play an important role in this respect. During haemodialysis (HD), both an increase in the expression of the platelet (PLT) cell surface molecule P-selectin (CD62p) and the release of intra-granular substances, such as platelet factor 4 (PF4) and ss-thromboglobulin (BTG), have been described. As the removal of uraemic toxins is superior during haemodiafiltration (HDF), this form of treatment may have quite another impact on PLTs than HD.


METHODS
Nineteen chronic HD patients who were treated with low-flux HD for at least 2 months were included in the Dutch CONvective TRAnsport STudy (CONTRAST). After randomization, 10 patients continued low-flux HD and 9 patients switched to post-dilution HDF. The present study describes various parameters of PLT activation and degranulation at baseline (during HD) and after 3 months (during HDF) in the latter group of patients. At both time points, multiple blood samples were drawn. During the first 30 min of treatment, differences over the extracorporeal circuit (ECC) were calculated by taking samples from both afferent (arterial) and efferent (venous) lines. Correlations between various parameters were calculated in the total group of patients after 3 months.


RESULTS
Immediately after the start of HD, PLT counts dropped over the ECC. During HDF, PLT counts decreased even more and reached a nadir at t30. CD62p expression increased early during HD and returned to baseline thereafter. During HDF, these changes were more pronounced and more protracted. With respect to degranulation, rather dissimilar results were obtained. During HD, both PF4 and BTG increased over time, whereas during HDF, PF4 increased but BTG did not change. Haemoconcentration and transmembrane pressure (TMP) within the dialyser were, respectively, approximately 10 and 3x higher during HDF than during HD. There was a striking correlation between the changes in haemoconcentration and the changes in both PLT counts and CD62p over the ECC.


CONCLUSIONS
PLT activation, as measured by the expression of CD62p, was more pronounced and more protracted during HDF than during HD. During HDF, PLTs were trapped abundantly within the ECC, not only after first passage, but also thereafter. The degranulation product BTG increased during HD, but did not change during HDF. These observations may well be explained by the greater haemoconcentration and/or higher TMP during HDF on the one hand, and superior convective transport at the other. Whether the potential harmful effects of enhanced PLT activation are counterbalanced by the beneficial effects of an increased convective transport of degranulation products remains to be established.
Gritters-van den Oever
Mareille
M
1Department of Nephrology, Medical Centre Alkmaar, Alkmaar, The Netherlands.
Grooteman
Muriel P C
MP
Bartels
Piet C M
PC
Blankestijn
Peter J
PJ
Bots
Michiel L
ML
van den Dorpel
Marinus A
MA
Schoorl
Marianne
M
Schoorl
Margreet
M
Ter Wee
Piet M
PM
Nubé
Menso J
MJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000502:physiology*; D015550:Cell Degranulation; D005112:Extracorporeal Circulation; D005260:Female; D017583:Hemodiafiltration; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation; D010976:Platelet Count; D010978:Platelet Factor 4 / Q000097:blood; D006435:Renal Dialysis; D001620:beta-Thromboglobulin / Q000032:analysis
D019007:P-Selectin; D001620:beta-Thromboglobulin; D010978:Platelet Factor 4