Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 91(05): 927-934
DOI: 10.1160/TH03-10-0645

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Localization of heparin and low-molecular-weight heparin in the rat kidney

Edward Young

¹Department of Pathology and Molecular Medicine, Hamilton, Ontario, Canada

³Department of Henderson Research, Centre, Hamilton, Ontario, Canada

,

Vivian Douros

³Department of Henderson Research, Centre, Hamilton, Ontario, Canada

,

Thomas J. Podor

¹Department of Pathology and Molecular Medicine, Hamilton, Ontario, Canada

³Department of Henderson Research, Centre, Hamilton, Ontario, Canada

,

Stephen G. Shaughnessy

¹Department of Pathology and Molecular Medicine, Hamilton, Ontario, Canada

³Department of Henderson Research, Centre, Hamilton, Ontario, Canada

,

Jeffrey I. Weitz

²Department of Medicine, McMaster University, Hamilton, Ontario, Canada

³Department of Henderson Research, Centre, Hamilton, Ontario, Canada

› Author Affiliations

Summary

Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) are cleared, at least in part, by the kidneys through a poorly understood process. This study was undertaken to explore the mechanism of renal clearance of these drugs. Rats were given fluorescein-5-isothiocyanate (FITC)-labeled UFH or LMWH intravenously. At intervals after injection, rats were euthanized and the kidneys were harvested and subjected to immunohistochemical analysis and fluorescence microscopy. Both UFH and LMWH were localized to renal tubular cells and no immunoperoxidase staining or fluorescence was detected in glomeruli. Autoradiography demonstrated similar intracellular distribution of radio-labeled UFH suggesting that this phenomenon is independent of the method used to label heparin. Fluoresence in the tubules increased as a function of time after UFH injection, but reached a plateau after LMWH injection suggesting that the rate of renal tubular uptake depends on the molecular size of the heparin. When administered prior to FITC-labeled UFH or LMWH, probenecid, a renal organic anion inhibitor, decreased the renal tubular uptake of the heparins, whereas cimetidine, a renal organic cation inhibitor, had no effect. These findings suggest that renal excretion of UFH and LMWH primarily reflects tubular uptake via an organic anion transport mechanism.

Keywords

Keywords

Low-molecular-weight heparin - unfractionated heparin - renal clearance - renal tubular cells

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