Dose-dependent movement of cationic molecules across the glomerular wall

Different concentrations of the polycation polyethyleneimine (PEI) were administered by single intravenous injections or by constant vascular perfusion to the kidneys of Sprague-Dawley rats. At a fixed time interval after administration of PEI, the kidneys were fixed and the distribution of PEI in the glomerular wall was evaluated by electron microscopy. At the lower concentrations (e.g., 0.005%), PEI bound only to the glomerular endothelial glycocalyx and preferentially to microvillous projections on this endothelium. At higher concentrations (e.g., 0.05%), PEI also bound to discrete anionic sites in the lamina rara interna (LRI) but was rarely seen in the lamina rara externa (LRE). As the concentration of PEI was further increased (e.g., 0.5%), PEI moved deeper into the glomerular basement membrane (GBM) and bound extensively to discrete anionic sites in the lamina rara externa. Although anionic sites in the LRI and LRE appeared nearly saturated following infusion of 0.5% PEI, this cationic molecule was rarely seen to cross filtration slits and pass into the urinary space. At still higher concentrations (e.g., 2%), however, PEI moved freely across the filtration slits, bound extensively to the glomerular epithelial glycocalyx, and induced a narrowing of the filtration slits. When PEI was mechanically perfused through the kidney vasculature for 3 minutes, PEI binding to the epithelial glycocalyx caused very extensive adherence of adjacent podocyte processes and the narrowing and loss of filtration slits. Also in these latter samples, discrete anionic sites in the LRE were no longer apparent and a dense band of PEI was seen under the foot processes.(ABSTRACT TRUNCATED AT 250 WORDS)