Localization and characterization of antithrombin in human kidneys

Antithrombin is a serine protease inhibitor that is critical in maintaining a thromboresistant vasculature. The association between low serum antithro mbin concentration and renal disease suggests;that the kidney plays a role in the conservation of plasma antithrombin. We used immunohistochemical tec hniques to determine the spatial distribution, heparin binding characterist ics, and intracellular and intercellular localization of antithrombin in bi opsy specimens (n = 53) of human donor kidneys obtained at the time of tran splantation. In the renal cortex, double antibody techniques demonstrated t he presence of intracellular antithrombin in proximal tubule epithelial cel ls. The reactivity was granular and was co-localized with vesicle-like stru ctures. Distal and collecting tubules did not demonstrate intraepithelial a ntithrombin reactivity. No tubule structures in the medullary region demons trated intracellular antithrombin, but all these structures showed intense basement membrane antithrombin reactivity. Double antibody techniques also demonstrated that the heparin binding domain of intraepithelial antithrombi n was occupied. Semiquantitative scores for intraepithelial antithrombin we re significantly decreased in renal biopsy specimens obtained 30 min after anastomosis compared with biopsies from the same organ obtained before anas tomosis. These findings suggest that antithrombin, probably in association with heparin or heparan sulfate, is internalized by renal proximal epitheli al cells. Although the ultimate fate of intraepithelial antithrombin is not known, this may represent a mechanism by which the kidney helps to maintai n plasma antithrombin concentrations.