Lipid microvesicles and their association with procoagulant activity in urine and glomeruli of rabbits with nephrotoxic nephritis.

The procoagulant activity (PCA) in urine of rabbits with nephrotoxic nephritis was characterized. Most of the PCA in urine was pelleted by centrifugation at 50,000 X g but was not pelleted together with cells and casts at 1,000 X g. PCA appeared in the void volume of a Sepharose 4B column but would not pass through a 0.2-micron filter. Ultrastructural studies using both transmission and scanning electron microscopy showed that urine PCA was associated with lipid vesicles 0.1 to 1-micron in diameter. These vesicular structures were shown to promote fibrin formation from recalcified plasma on a 0.2-micron filter surface. This microvesicular PCA was mostly Factor VII-like as judged by clotting assay using human factor-deficient plasmas. Aggregates of vesicles were present in urine as granular casts. Ultrastructural studies of rabbit kidney showed similar vesicular structures in the proximal tubular lumen and budding from glomerular epithelial cells. Fibrin was seen adjacent to both glomerular endothelial cells and epithelial cells in association with vesicular structures. We conclude that microvesicles in urine carry a procoagulant signal which is tissue factor/Factor VII-like. We speculate that these vesicles may come from the glomerulus by budding off from glomerular epithelial cells, or macrophages.