Apical transport of drugs in the proximal tubule.

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Presentation transcript:

Apical transport of drugs in the proximal tubule. Apical transport of drugs in the proximal tubule. (A) Aminoglycosides Apical membrane handling of substances, in this example aminoglycosides, by proximal tubular cells increases cellular uptake of this nephrotoxic drug. Polycationic aminoglycosides are attracted to the anionic phospholipid membranes where they interact with megalin-cubilin receptor on the apical surface. The aminoglycosides are endocytosed and enter the cell where they are translocated into lysosomes. Lysosomal injury and rupture along with mitochondrial injury result in tubular cell injury. (B) Hydroxyethyl starch. Apical membrane handling of hydroxyethyl starch by proximal tubular cells increases cellular uptake of this potentially nephrotoxic drug. Hydroxyethyl starch as well as sucrose (carrier for IVIg), dextran, and mannitol undergo pinocytosis and enter the cell where they are translocated into lysosomes. The lack of enzymes necessary to metabolize these substances allows accumulation within lysosomes, which causes cell swelling (occluding tubular lumens) and eventual lysosomal rupture resulting in tubular cell injury. AG, aminoglycosides; HES, hydroxyethyl starch; IVIg, intravenous immunoglobulin; K+, potassium; MC, megalin-cubilin; Na+, sodium; PL, anionic phospholipids. Mark A. Perazella CJASN 2018;13:1897-1908 ©2018 by American Society of Nephrology