OBJECTIVE To evaluate glomerular charge selectivity in patients with type 2 diabetes, we studied changes in fractional clearance of proteins with different sizes and charges when patients were placed on two diets with different salt contents.

RESEARCH DESIGN AND METHODS Nineteen patients with type 2 diabetes and normoalbuminuria (<20 μg/min, n = 8), microalbuminuria (20–100 μg/min, n = 7), or advanced albuminuria (>100 ug/min, n = 4) were placed on a low-salt diet (85 mEq of sodium daily) or a high-salt diet (255 mEq of sodium daily) for 1 week, and then on the other diet, in random order. Fractional clearances of albumin and immunoglobulin G (IgG) were calculated on the last 3 days of each diet.

RESULTS In patients with normoalbuminuria, the high-salt diet increased the fractional clearance of IgG, which is electrically neutral, but the fractional clearance of albumin, which is anionic, was unaltered, suggesting that the pore charge of the glomerular barrier was unaffected. However, in patients with microalbuminuria, the high-salt diet increased the fractional clearances of IgG and albumin equally, indicating some neutralization of the pore charge. Fractional clearance of IgG in these first two groups was similar when salt intake was low, so pore size was the same in these groups. In patients with advanced albuminuria, fractional clearance of IgG was higher than in the other groups, indicating that size selectivity had worsened.

CONCLUSIONS In type 2 diabetic patients, charge selectivity is lost before size selectivity as diabetic nephropathy progresses.