PMID- 14633147
OWN - NLM
STAT- MEDLINE
DCOM- 20040716
LR  - 20061115
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 64
IP  - 6
DP  - 2003 Dec
TI  - Activation of hepatocyte growth factor/activin A/follistatin system during 
      hemodialysis: role of heparin.
PG  - 2229-37
AB  - BACKGROUND: Hepatocyte growth factor (HGF), activin A, and follistatin compose an 
      organotrophic system that may be modulated by heparin. We prospectively studied 
      the effects of unfractionated heparin (UFH) versus low-molecular-weight heparin 
      (LMWH) enoxaparin-anticoagulated hemodialysis on plasma levels of the cytokines. 
      METHODS: The factors were measured by immunoassays in 25 chronic hemodialysis 
      patients at the start and at 10 and 180 minutes of the hemodialysis procedure 
      anticoagulated with bolus enoxaparin. Then, the patients were randomized to 
      either receive a bolus and infusion of UFH or to continue LMWH, and were 
      reexamined after 12 weeks. RESULTS: Predialysis HGF and follistatin were 
      increased (both P < 0.0001), while activin A was normal in hemodialysis patients. 
      Baseline HGF directly correlated with activin A in hemodialysis subjects 
      (P=0.004). In healthy controls, it was positively associated with follistatin 
      (P=0.001). Both HGF and activin A were markedly increased at each interval of 
      enoxaparin-anticoagulated hemodialysis, and follistatin was increased at 10 
      minutes (all P < 0.0001). The early increments in HGF and follistatin directly 
      depended on the dose of enoxaparin (both P < 0.030). Remarkably, the rise in 
      activin A was inversely associated with the predialysis level of the cytokine (P 
      < 0.0001). The actions of UFH resembled those of LMWH, although the releasing 
      effects on the growth factors were not dose-dependent. The switch from LMWH to 
      UFH resulted in a significant increase in over-dialysis HGF, a fall in 
      follistatin, and no change in activin A. CONCLUSION: HGF/activin A/follistatin 
      system is activated and disturbed in chronic hemodialysis patients, including 
      depletion of tissue stores of activin A. Type and dose of heparin used during 
      hemodialysis procedures profoundly influence this pleiotropic system, and may 
      thus modulate vital body functions and course of critical diseases.
FAU - Borawski, Jacek
AU  - Borawski J
AD  - Department of Nephrology and Internal Medicine, Medical University, Bialystok, 
      Poland. jborawski@post.pl
FAU - Naumnik, Beata
AU  - Naumnik B
FAU - Mysliwiec, Michal
AU  - Mysliwiec M
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Anticoagulants)
RN  - 0 (Enoxaparin)
RN  - 0 (Follistatin)
RN  - 0 (activin A)
RN  - 104625-48-1 (Activins)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 9005-49-6 (Heparin)
RN  - 93443-12-0 (Inhibin-beta Subunits)
SB  - IM
CIN - Kidney Int. 2004 Jul;66(1):465. PMID: 15200470
MH  - Activins/blood/*metabolism
MH  - Aged
MH  - Anticoagulants/*therapeutic use
MH  - Enoxaparin/*therapeutic use
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Follistatin/blood/*metabolism
MH  - Heparin/*therapeutic use
MH  - Hepatocyte Growth Factor/blood/*metabolism
MH  - Humans
MH  - Inhibin-beta Subunits/blood/*metabolism
MH  - Kidney Diseases/blood/metabolism/therapy
MH  - Male
MH  - Middle Aged
MH  - *Renal Dialysis
EDAT- 2003/11/25 05:00
MHDA- 2004/07/17 05:00
CRDT- 2003/11/25 05:00
PHST- 2003/11/25 05:00 [pubmed]
PHST- 2004/07/17 05:00 [medline]
PHST- 2003/11/25 05:00 [entrez]
AID - S0085-2538(15)49593-6 [pii]
AID - 10.1046/j.1523-1755.2003.00307.x [doi]
PST - ppublish
SO  - Kidney Int. 2003 Dec;64(6):2229-37. doi: 10.1046/j.1523-1755.2003.00307.x.