Hepatocyte Growth Factor/Activin A/Follistatin System Activation during Hemodialysis with Different Low Molecular Weight Heparins

Abstract

Hepatocyte growth factor (HGF), activin A (Act A), and follistatin (FS) compose an organotrophic system; interestingly it is modified by heparin. To understand if LMWHs (considered distinct drugs) have different clinical profiles regarding the above growth factors, we studied the effects of enoxaparin, nadroparin, and dalteparin on their plasma levels. Seventeen chronic HD patients completed this prospective, crossover trial. They were randomized into six groups: each patient was administered enoxaparin (effective dose of 0.75 mg/kg), nadroparin (70.4 IU/kg) and dalteparin (78.6 IU/kg) in three time periods of two months each. At the end of this period, the cytokine's plasma levels were measured by immunoassays at the start and at 10 min and 180 min of the HD procedure. At 10 min, we observed a striking increase in plasma HGF (32-fold), Act A (4-fold), and FS (53%), all p = 0.0003. The levels of HGF and Act A remained markedly elevated after 180 min (by 295% and 87%, respectively; both p < 0.002), while those of FS returned to baseline. There were no differences in cytokine profile comparing both their peak concentrations and the areas under the curve. Enoxaparin, dalteparin, and nadroparin are seemingly not different considering the release of HGF/Act A/FS during HD procedures; this may reflect their similar profile in other aspects. Moreover, the concentrations of HGF/Act A/FS are close to therapeutic ones, which may partly explain the mechanisms underlying some of the emerging extra-anticoagulant effects of LMWHs.