von Willebrand Factor expression in a Shiga toxin-mediated primate model of hemolytic uremic syndrome.

von Willebrand Factor (vWF) is stored and released from activated or damaged endothelial cells and platelets, and its multimers have considerable prothrombotic properties. To investigate the role of vWF in the pathogenesis of post-diarrheal (D+) hemolytic uremic syndrome (HUS), we used a baboon model to study vWF expression following the intravenous administration of 100 ng/kg of Shiga toxin 1 (Stx 1), given either as a single dose, or as four divided doses, with and without lipopolysaccharide (LPS). vWF antigen was measured in plasma and urine obtained at 0, 12, 24, 36, 48, and 60 h by enzyme-linked immunosorbent assay (ELISA), and immunohistochemical expression of vWF in renal tissue obtained at autopsy was quantified by image analysis. Animals that received the single dose of Stx 1, or the four divided doses of Stx 1 plus LPS uniformly developed HUS, but those that received divided doses of Stx 1 without LPS, or LPS alone did not. Plasma vWF levels rose significantly in animals that received LPS, with or without Stx 1; but not in those that received Stx 1 alone. Urine vWF levels were generally undetectable. vWF expression was greater in renal tissue of animals that developed HUS than in those that did not, and was seen in both glomeruli, and, especially, peritubular capillaries. Since HUS developed in animals that did not experience a rise in plasma vWF levels, it does not appear that LPS-mediated systemic vWF release is essential to the pathogenesis of HUS in our model. The renal tissue findings, however, suggest a role for Stx-mediated intrarenal vWF release in the acute nephropathy of D+ HUS.