Human uremic plasma increases microvascular permeability to water and proteins in vivo

Abstract

Background. The risk of cardiovascular disease is significantly higher in patients with long-term uremia than in otherwise healthy adults. This is true even before patients proceed to dialysis, but the reason why cardiovascular risk is increased is unknown. Transvascular transport of lipids and other macromolecules in both large vessels and the microcirculation has been implicated in generation of cardiovascular disease. Methods. To determine whether patients with long-term uremia have circulating factors that promote increased vascular permeability, we measured the effect of perfusing microvessels with uremic plasma in a non-mammalian model of vascular permeability measurement. Results. Perfusion of frog mesenteric microvessels with dialyzed normal plasma did not result in an increase in either hydraulic conductivity (Lp, permeability of the vessel wall to water) or oncotic reflection coefficient (σ, permeability to macromolecules, particularly proteins). Perfusion with dialyzed uremic plasma resulted in a very significant increase in vascular permeability to both water (Lp increased 8.8-fold from 4.1 to 36.4 × 10-7 cm s-1 cm H2O-1) and proteins (σ reduced from 0.93 to 0.53). Conclusions. These results suggest that one or more circulating macromolecules in uremic plasma are able to increase transvascular solute and fluid flux, and may underlie the increased cardiovascular risk found in these patients.