MECHANISMS OF PROTEINURIA IN NEPHROTIC HUMANS

The glomerular capillary wall imposes a remarkably efficient barrier t o the passage of proteins the size of albumin and larger. The developm ent of heavy proteinuria signifies impairment of the function of this barrier. Because endogenous proteins of graded size are heterogeneous with respect to their molecular charge and undergo extensive tubular r eabsorption, they are not useful for quantifying the extent of barrier dysfunction. An alternative approach is to determine the fractional c learance of uncharged and non-reabsorbable polymers of graded size. Wh en combined with a hydrodynamic theory of solute transport through a h eteroporous membrane, the intrinsic properties of healthy and diseased glomerular capillary walls can be inferred. This approach reveals the nephrotic range proteinuria that attends minimal change nephropathy t o be associated with impairment of both the size- and charge-selective properties of glomerular capillary walls.