MOLECULAR-CONFIGURATION AND GLOMERULAR SIZE-SELECTIVITY IN HEALTHY AND NEPHROTIC HUMANS

We studied eight healthy volunteers and eight nephrotic subjects to co mpare the glomerular sieving coefficients (theta) of dextran, a linear polymer of glucopyranose, with those of Ficoll, a spherical polysucro se. Over a molecular radius (r(s)) interval of 20-70 Angstrom, theta f or a given Ficoll was uniformly lower than corresponding theta for a d extran of equivalent r(s). For each macromolecular species, the theta of molecules with r(s) > 50 Angstrom was selectively enhanced in nephr otic vs. healthy subjects. Analysis of either dextran or Ficoll sievin g curves with pore theory revealed the glomerular barrier to have a bi modal pore size distribution: a lower mode of restrictive pores with a lognormal distribution of radii and an upper mode of large shuntlike pores. Nephrotics differed from controls in that the lower mode was br oadened and shifted to pores of smaller mean size, but the prominence of shuntlike pores was enhanced by an order of magnitude. Both the mea n radius of restrictive pores and the magnitude of the shunt pathway w ere substantially smaller when estimated from Ficoll than dextran siev ing. We interpret the more realistic values for pore parameters derive d from Ficoll than dextran sieving to indicate 1) that the normal glom erular barrier prevents albuminuria by virtue of a combination of both charge-and size-selective properties and 2) that a combined impairmen t of both barrier charge selectivity and size selectively are required to account for the observed level and composition of proteinuria in o ur nephrotic subjects.