NDT Advance Access published online on March 26, 2007
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfm082
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Enoxaparin but not unfractionated heparin causes a dose-dependent increase in plasma TGF-ß1 during haemodialysis: a cross-over study
My
liwiec
Department of Nephrology and Transplantation with Dialysis Unit, Medical University, Biaystok, Poland
Correspondence and offprint requests to:
Beata Naumnik, Department of Nephrology and Transplantation with Dialysis Unit, Medical University, 14 
urawia St, 15-540 Biaystok, Poland. Email: bnaumnik{at}poczta.onet.pl
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Abstract |
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Background. Transforming growth factor-ß1 (TGF-ß1) 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-ß1 levels and some platelet activation markers: platelet-derived growth factor–AB (PDGF-AB), ß-thromboglobulin (ß-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-ß1 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-ß1 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-ß1 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-ß1 and PDGF-AB during HD, there were no associations between TGF-ß1 and ß-TG or PF-4 regardless of the type of anticoagulation.
Conclusion. Enoxaparin, compared with UFH, induces a rapid overdialytic but not sustained increase in plasma TGF-ß1 levels. The effect is closely dose-dependent and may reflect systemic activation of this multi-potential cytokine.
Keywords: enoxaparin; haemodialysis; transforming growth factor-ß1; unfractionated heparin
Received for publication: 10.12.06
Accepted in revised form: 26. 1.07
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