An average 15-fold increase in lactosylceramide (LacCer) in the sediment of receptor-negative, familial hypercholesterolemic (FH) homozygotes has been reported. We report here the abnormal urinary excretion of significant numbers of renal tubular cells in eight FH homozygotes. The mean activity of γ-glutamyltransferase, a marker for renal tubular cells, was twice as high in urinary sediment of FH homozygotes as in normals. Membrane-enclosed cytoplasmic vesicles that stained strongly positive with a fluorescein-labeled antibody against LacCer were found in the renal tubular cells of all homozygotes except two who had undergone a portacaval shunt. These two had normal urinary levels of LacCer, and the cytoplasmic vesicles were vacuolated. In the other six, most of the fluorescent antibody label was intracellular and perinuclear. The cytoplasmic vesicles stained strongly with polychromatic Papanicolaou stain, periodic acid/Schiff reagent, and oil red O. Electron microscopy revealed perinuclear membrane-enclosed lipid and free lipid droplets. When two FH homozygotes, who excreted increased LacCer, underwent plasma exchange, the cytoplasmic vesicles became empty, and the urinary LacCer level decreased into the normal range. We conclude that the increased urinary excretion of LacCer in FH homozygotes occurs in renal tubular cells and that the intracellular location of LacCer is within cytoplasmic vesicles. The presence of LacCer within these vesicles can be modulated by treatment with plasma exchange.
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