REDUCED GLOMERULAR SIZE-SELECTIVITY AND CHARGE-SELECTIVITY IN CLINICALLY HEALTHY-INDIVIDUALS WITH MICROALBUMINURIA

The pathophysiologic mechanism behind microalbuminuria, a potential at herosclerotic risk factor, was explored by measuring fractional cleara nces of four endogenous plasma proteins of different size and electric charge (albumin, beta(2)-microglobulin, immunoglobulin G, and immunog lobulin G(4)) Twenty-eight clinically healthy individuals with microal buminuria, defined as a urinary albumin excretion of 6.6-150 mu g min( -1), and 60 matched control subjects were studied. Fractional immunogl obulin G clearance was higher (geometric means (95% confidence interva ls)) 3.0 (2.3-3.9) x 10(-6), n=28; vs. 2.1 (1.8-2.4) x 10(-6) n=60; P= 0.02), whereas the ratio immunoglobulin G clearance/immunoglobulin G(4 ) clearance was lower (geometric means (95% confidence intervals)) 1.8 (1.4-2.2), n=28, vs. 2.3 (2.0-2.5), n=60; P=0.03) in microalbuminuric than in normoalbuminuric individuals. Fractional beta(2)-microglobuli n clearance was similar in the two groups. Since total IgG and the IgG (4) subclass are of similar size and configuration but electrically ne utral and negative, respectively; these findings indicate that microal buminuria is associated with decreased size- and charge-selectivity of the glomerular vessel wall. Hypothetically, such alterations may refl ect generalized vascular abnormalities linking microalbuminuria to ath erogenesis.