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

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.