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

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Abstract
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, β2‐microglobulin, immunoglobulin G, and immunoglobulin G4). Twenty‐eight clinically healthy individuals with microalbuminuria, defined as a urinary albumin excretion of 6.6–150μg 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) × 10‐6, n= 28, vs. 2.1 (1.8–2.4) × 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 β2‐micro‐globulin 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. Hypotheti‐cally, such alterations may reflect generalized vascular abnormalities linking microalbuminuria to athero‐genesis.

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