Influence of hypersulfated and low molecular weight heparins on ischemia/reperfusion: injury and allograft rejection in rat kidneys.
The aim of the study was to evaluate the effect of the hypersulfated nonanticoagulant heparin derivative LU 51198 (LU) and of the low molecular weight heparin reviparin (REVI) on ischemia/reperfusion (I/R) injury, acute rejection (AR) and chronic allograft nephropathy (CAN) in rats. Organs were harvested 5 days after 60 min of renal I/R injury. For investigation of AR and CAN we used the allogeneic Fisher-Lewis model. Kidneys were harvested at one respectively 32 weeks after transplantation. Rats were treated with either vehicle, LU or REVI. After I/R injury, treatment with REVI or LU reduced infiltration with MHC II and R73-positive cells, whereas only REVI reduced ED1-positive cells and expression of monocyte chemoattractant protein-1. There was no effect of REVI and LU on acute allograft rejection. Treatment with LU or REVI reduced glomerular infiltration with ED1 and MHCII-positive cells and renal expression of transforming growth factor-beta 32 weeks after transplantation. Only REVI treatment reduced albuminuria, interstitial infiltration and histological signs of CAN. LU, and in a more potent manner REVI, reduce signs of CAN and renal inflammation after I/R injury. Chemically modified heparins without anticoagulatory effects may offer a new treatment option in preventing I/R injury and CAN in human kidney transplantation.
Gottmann
Uwe
U
V. Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Hospital Mannheim, University of Heidelberg, Mannheim, Germany. uwe.goettmann@med5.ma.uni-heidelberg.de
Mueller-Falcke
Astrid
A
Schnuelle
Peter
P
Birck
Rainer
R
Nickeleit
Volker
V
van der Woude
Fokko J
FJ
Yard
Benito A
BA
Braun
Claude
C
D000419:Albuminuria / Q000188:drug therapy / Q000517:prevention & control; D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D006084:Graft Rejection / Q000188:drug therapy*; D006493:Heparin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D007668:Kidney / Q000473:pathology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000188:drug therapy*; D016896:Treatment Outcome
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; C107689:LU 51198; C094240:reviparin; D006493:Heparin