title: Influence of hypersulfated and low molecular weight heparins on ischemia/reperfusion: injury and allograft rejection in rat kidneys.
abstract: 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.
authors.affiliation: V. Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Hospital Mannheim, University of Heidelberg, Mannheim, Germany. uwe.goettmann@med5.ma.uni-heidelberg.de
authors.forename: Uwe
authors.initials: U
authors.lastname: Gottmann
authors.forename: Astrid
authors.initials: A
authors.lastname: Mueller-Falcke
authors.forename: Peter
authors.initials: P
authors.lastname: Schnuelle
authors.forename: Rainer
authors.initials: R
authors.lastname: Birck
authors.forename: Volker
authors.initials: V
authors.lastname: Nickeleit
authors.forename: Fokko J
authors.initials: FJ
authors.lastname: van der Woude
authors.forename: Benito A
authors.initials: BA
authors.lastname: Yard
authors.forename: Claude
authors.initials: C
authors.lastname: Braun
mesh_terms: 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
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; C107689:LU 51198; C094240:reviparin; D006493:Heparin