Glomerular charge alterations in human minimal change nephropathy

A theoretical model of charge and size selectivity for the glomerulus has been applied to human data. Using previously published values for GFR, renal plasma flow, systemic oncotic pressure, and fractional clearance of neutral dextrans, albumin, salivary amylase, and transferrin, membrane parameters describing the glomerular barrier were determined for normal individuals under control conditions and during lysine infusion (which retards tubule protein reabsorption), and for patients with minimal change nephropathy (MCN). To permit the estimation of membrane charge fractional clearances, molecular charge values for human transferrin (-9.4 Eq/mole) and human salivary amylase (-4.1) were determined by measuring electrophoretic mobilities of these proteins in polyacrylamide gels. Assuming no large changes in the transmural hydraulic pressure difference (ΔP), the glomerular ultrafiltration coefficient (K(f), the product of hydraulic permeability and capillary surface area) was calculated to be reduced by > 50% in MCN. The effective pore radius (~55 Å) is virtually unaltered in MCN, suggesting that the decline in K(r) is due to a reduced number of pores. The degree of albuminuria observed in MCN is attributable to an approximately 50% reduction in the concentration of fixed negative charges in the glomerular capillary wall. The concentrations of fixed charges calculated from albumin data in normal individuals (140 to 160 mEq/liter) and in patients with MCN (60 to 90 mEq/liter) are insensitive to the assumed values of ΔP.