Renal and Systemic Transvascular Albumin Leakage in Severe Atherosclerosis

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Abstract
Abstract Microalbuminuria was recently proposed as a novel atherogenic risk factor. The pathophysiological link between microalbuminuria and atherosclerosis may be mediated through an increased generalized transvascular leakage of albumin. To investigate this hypothesis, urinary albumin excretion and clearance and systemic transvascular albumin leakage (TER alb ) were measured in 23 patients with severe clinical atherosclerosis and 25 healthy controls. In addition, renal clearances of three other endogenous plasma proteins (IgG, IgG 4 , and β 2 -microglobulin) and of creatinine were measured. Measurements of urine and serum proteins were done by enzyme-linked immunosorbent assays. TER alb was measured by the fractional disappearance rate of 125 I-albumin from the total intravascular compartment in 1 hour after intravenous injection. Glomerular filtration rate was estimated as creatinine clearance. Urinary albumin excretion (geometric means [95% confidence intervals], 10.5 [6.1 to 18.3] versus 5.7 [4.7 to 6.9] μg/min; P <.05), fractional urinary albumin clearance (2.8 [1.6 to 4.8] ×10 −6 versus 1.3 [1.0 to 1.6] ×10 −6 ; P <.05), and TER alb (6.0 [5.5 to 6.5] versus 5.1 [4.5 to 5.8] %/h; P <.05) were higher in patients than in control subjects. Glomerular charge selectivity (ratio of IgG clearance to IgG 4 clearance) was lower in patients than in control subjects (1.5 [1.1 to 2.0] versus 2.3 [2.0 to 2.6]; P <.05). These alterations were independent of blood pressure, glomerular filtration rate, tubular function, and smoking status. It is concluded that atherosclerotic vascular disease is associated with renal and systemic transvascular leakiness for albumin. Theoretically, such leakiness may in addition allow for an increased lipid insudation into the large vessel wall, thereby linking microalbuminuria to atherogenesis. The lower glomerular charge selectivity is suggestive of decreased concentration of anionic components in the vessel walls.

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