Normal glomerular permeability and its modification by minimal change nephrotic syndrmone

Area of Science:

• Nephrology
• Renal Physiology
• Molecular Biology

Background:

• The glomerular basement membrane was historically considered the primary filter for large molecules.
• The role of the epithelial slit pore as a filtration barrier for smaller molecules remained debated.

Purpose of the Study:

• To investigate the filtration barrier function in idiopathic nephrotic syndrome (INS).
• To determine if the epithelial slit pore restricts the passage of smaller molecules.

Main Methods:

• Measured glomerular permeability to polyvinyl pyrrolidone (PVP) of varying molecular sizes in children with INS and healthy controls.
• Analyzed PVP in blood and urine using column chromatography.
• Assessed changes before, during, and after steroid treatment in INS patients.

Main Results:

• Untreated INS showed normal permeability to larger molecules (>40 Å) but reduced permeability to smaller molecules.
• Glomerular permeability and inulin clearance (C(in)) normalized with steroid treatment only after proteinuria resolved.
• Fusion of epithelial foot processes correlated with impaired passage of smaller PVP molecules.

Conclusions:

• The epithelial slit pore functions as the final filtration barrier for smaller molecules.
• Observed decreases in C(in) in INS may be due to restricted passage through slit pores, not solely reduced glomerular filtration rate.
• Reversal of podocyte abnormalities restores normal filtration barrier function.