Enoxaparin but not unfractionated heparin causes a dose-dependent increase in plasma TGF-beta 1 during haemodialysis: a cross-over study.
BACKGROUND
Transforming growth factor-beta1 (TGF-beta1) is a multi-functional cytokine that presents as a mediator of the heparin's pleiotropic action. In this cross-over study, we compared the effects of enoxaparin and unfractionated heparin (UFH) used as anticoagulants during haemodialysis (HD) on plasma TGF-beta1 levels and some platelet activation markers: platelet-derived growth factor-AB (PDGF-AB), beta-thromboglobulin (beta-TG) and platelet factor-4 (PF-4).


METHODS
Plasma immunoreactive markers (in 22 chronically HD patients) were quantified at the start, at 10 and 180 min of HD session. Enoxaparin was administered as a single dose of 0.67 +/- 0.14 mg/kg at the onset of HD, while UFH was given as a bolus of 1500 (500-3500) IU followed by an infusion of 2750 (1500-6500) IU. The time of evaluation for each heparin was 3 months.


RESULTS
Pre-dialysis, TGF-beta1 levels tended to be lower in patients anticoagulated with enoxaparin compared with UFH [6.9 (3.3-21.9) ng/ml vs 8.4 (3.8-30.2) ng/ml, respectively; P = 0.05]. Overdialysis, TGF-beta1 levels showed a significant 44.8% increase to 10.0 (2.9-28.0) ng/ml after 10 min (P = 0.002) and to 9.32 (5.3-23.7) ng/ml after 180 min (P = 0.016) of enoxaparin-anticoagulated HD and remained stable during UFH administration [9.4 (3.9-25.3) ng/ml after 10 min, 8.1 (4.1-21.9) ng/ml after 180 min; P = 0.385]. The 35% increase in plasma TGF-beta1 after 180 min of HD positively correlated with the enoxaparin dose/kg (r = 0.553, P = 0.008) and, interestingly, negatively with the baseline level of the cytokine (r = -0.544, P = 0.009). Despite a positive correlation between TGF-beta1 and PDGF-AB during HD, there were no associations between TGF-beta1 and beta-TG or PF-4 regardless of the type of anticoagulation.


CONCLUSIONS
Enoxaparin, compared with UFH, induces a rapid overdialytic but not sustained increase in plasma TGF-beta1 levels. The effect is closely dose-dependent and may reflect systemic activation of this multi-potential cytokine.
Naumnik
Beata
B
Department of Nephrology and Transplantation with Dialysis Unit, Medical University, 14 Zurawia Street, 15-540 Białystok, Poland. bnaumnik@poczta.onet.pl
Borawski
Jacek
J
Pawlak
Krystyna
K
Mysliwiec
Michal
M
D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D017984:Enoxaparin / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006493:Heparin / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D006435:Renal Dialysis; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000097:blood*
D000925:Anticoagulants; D017984:Enoxaparin; D053773:Transforming Growth Factor beta1; D006493:Heparin