Reduced glomerular size- and charge-selectivity in clinically healthy individuals with microalbuminuria

The pathophysiologic mechanism behind microalbuminuria, a potential atherosclerotic risk factor, was explored by measuring fractional clearances of four endogenous plasma proteins of different size and electric charge (albumin, beta 2-microglobulin, immunoglobulin G, and immunoglobulin G4). Twenty-eight clinically healthy individuals with microalbuminuria, defined as a urinary albumin excretion of 6.6-150 micrograms min-1, and 60 matched control subjects were studied. Fractional immunoglobulin G clearance was higher (geometric means (95% confidence intervals)) 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 G4 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-microglobulin clearance was similar in the two groups. Since total IgG and the IgG4 subclass are of similar size and configuration but electrically neutral and negative, respectively; these findings indicate that microalbuminuria is associated with decreased size- and charge-selectivity of the glomerular vessel wall. Hypothetically, such alterations may reflect generalized vascular abnormalities linking microalbuminuria to atherogenesis.