TUBULAR LIPIDOSIS - EPIPHENOMENON OR PATHOGENETIC LESION IN HUMAN RENAL-DISEASE

Tubular lipidosis is a commonly observed histological lesion in protei nuric renal diseases. We have studied the interaction between native a nd modified human lipoproteins and human renal proximal tubular cells to investigate whether lipoproteins could be injurious to tubular cell s in culture. Human renal proximal tubular cells were cultured and cha racterized by established methods. Preliminary studies showed that the se cells could take up and degrade normal human lipoproteins by high a ffinity (HDL) and low affinity (LDL) pathways. In subconfluent culture , native lipoproteins, that is, LDL, HDL(2) and HDL(3), had markedly d ifferent effects on cell growth as measured by H-3-thymidine uptake an d total cell protein as compared to modified lipoproteins such as mini mally modified and oxidized LDL. In addition, we found that renal tubu lar cells could oxidize native LDL in the presence of copper largely b y a superoxide-mediated mechanism. Finally, cellular accumulation of l ipid was demonstrated in vitro by incubating cultured cells with varyi ng lipoprotein concentrations for up to 48 hours. Notably, cell detach ment was observed only with high concentrations of modified LDL especi ally with minimally modified LDL. We speculate that uptake and oxidati on of filtered LDL by tubular cells may lead to tubular injury in neph rotic states.