Fractional clearances of uncharged
dextran 40 and anionic
proteins were performed in an attempt to elucidate the defect in glomerular barrier function responsible for heavy
proteinuria in
diabetic nephropathy. Notwithstanding urinary
albumin excretion (UalbV) at 3634 +/- 608 microgram/min, the fractional clearance for
dextran molecules with Einstein-Stokes radii (r) between 22 and 36 A was depressed in 12 patients with advanced
diabetic nephropathy, which suggests a reduction in mean glomerular pore size or density. Equivalent restriction to transglomerular passage of
dextrans with a r < 36 A in 7 patients with
minimal change nephropathy was associated with a similarly enhanced
proteinuria (UalbV, 3333 +/ 759 microgram/min). The dissociation between fractional clearances for neutral and anionic macromolecules in both disorders is consistent with loss of glomerular electrostatic charge. In
diabetic nephropathy, however, the fractional clearances for large
dextrans and test
proteins considerably exceeded corresponding values in
minimal change nephropathy when r greater than or equal to 36 A. Furthermore, the fractional clearances for test
proteins were two orders of magnitude smaller than that for equivalent-sized
dextrans in
minimal change nephropathy, whereas this difference was much less in
diabetic nephropathy. Thus, a selective increase in transglomerular passage of large molecules and a progressive loss of ability to discriminate between large molecules of different configuration distinguish the glomerular capillary wall in
diabetic nephropathy from that in
minimal change nephropathy.