PMID- 17389624 OWN - NLM STAT- MEDLINE DCOM- 20070817 LR - 20070528 IS - 0931-0509 (Print) IS - 0931-0509 (Linking) VI - 22 IP - 6 DP - 2007 Jun TI - Enoxaparin but not unfractionated heparin causes a dose-dependent increase in plasma TGF-beta 1 during haemodialysis: a cross-over study. PG - 1690-6 AB - 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. CONCLUSION: 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. FAU - Naumnik, Beata AU - Naumnik B AD - Department of Nephrology and Transplantation with Dialysis Unit, Medical University, 14 Zurawia Street, 15-540 Bialystok, Poland. bnaumnik@poczta.onet.pl FAU - Borawski, Jacek AU - Borawski J FAU - Pawlak, Krystyna AU - Pawlak K FAU - Mysliwiec, Michal AU - Mysliwiec M LA - eng PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20070326 PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 0 (Anticoagulants) RN - 0 (Enoxaparin) RN - 0 (Transforming Growth Factor beta1) RN - 9005-49-6 (Heparin) SB - IM MH - Aged MH - Anticoagulants/administration & dosage/*therapeutic use MH - Cross-Over Studies MH - Dose-Response Relationship, Drug MH - Enoxaparin/administration & dosage/*therapeutic use MH - Female MH - Heparin/*administration & dosage MH - Humans MH - Male MH - *Renal Dialysis MH - Transforming Growth Factor beta1/biosynthesis/*blood EDAT- 2007/03/29 09:00 MHDA- 2007/08/19 09:00 CRDT- 2007/03/29 09:00 PHST- 2007/03/29 09:00 [pubmed] PHST- 2007/08/19 09:00 [medline] PHST- 2007/03/29 09:00 [entrez] AID - gfm082 [pii] AID - 10.1093/ndt/gfm082 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2007 Jun;22(6):1690-6. doi: 10.1093/ndt/gfm082. Epub 2007 Mar 26.