Normal Glomerular Permeability and Its Modification by Minimal Change Nephrotic Syndrome

Abstract

It has been suggested that the glomerular basement membrane restricts the passage of large molecules only, the barrier to filtration of smaller molecules being at the level of the epithelial slit pore. This hypothesis was investigated by measuring glomerular permeability to ¹²⁵I-labeled polydisperse polyvinyl pyrrolidone (PVP) in 16 children with idiopathic nephrotic syndrome (INS) and in 6 children of comparable age who had no evidence of renal disease. Studies were performed in the patients with INS before, during, and after treatment with steroids. PVP in blood and urine samples was separated according to molecular size by solumn chromatography, to permit the calculation of permeability to inert macromolecules of sizes ranging from 8,000 mol wt. In untreated INS, glomerular permeability to molecules > 40 Å was normal; permeability to smaller molecules was markedly reduced, frequently to 20% or less of normal. There was an average decrease in inulin clearance (C_in) of 24%. Glomerular permeability and C_in returned to normal in INS treated with steroids only when proteinuria disappeared. The results support the concept, derived from studies with ultrastructural tracers, that the final barrier to filtration may be at the level of the epithelial slit pore. Thus fusion of the epithelial foot processed with obliteration of the slit pores was associated with impaired passage of smaller molecules of PVP into the urine. Reversal of the pathologic abnormality resulted in return of permeability to normal. The decreased C_in seen in INS may not reflect true glomerular filtration rate, but may result from restricted passage of inulin molecules (mol wt 5,000) through the epithelial slit pore.