Journal
TRANSPLANT INTERNATIONAL
Volume 20, Issue 6, Pages 542-549Publisher
BLACKWELL PUBLISHING
DOI: 10.1111/j.1432-2277.2007.00471.x
Keywords
acute rejection; chronic rejection; heparin; kidney; ischemia/reperfusion; rat
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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.
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