Proteinuria induced by sodium maleate in rats: Effects on ultrastructure and protein handling in renal proximal tubule

Abstract

We studied the effects of sodium maleate on renal handling of protein in rats injected i.v. with sodium maleate. We used lysozyme (mol wt, 14,400 daltons) labeled with iodine 125 as a tracer. We studied the protein reabsorption and transport in the renal proximal tubule cells, electron microscope autoradiography, and we followed the lysosomal digestion of lysozyme in renal cortical slices. Maleate decreased glomerular filtration and tubular reabsorption of lysozyme but caused an increased urinary excretion. The digestion of reabsorbed lysozyme was considerably reduced in renal cortical slices, and autoradiography revealed that the transport of protein from endocytic vacuoles to lysosomes in proximal tubule cells was partially inhibited. After maleate treatment, endocytic vacuoles rapidly accumulated in the apical cytoplasm membrane. An ultrastructural morphometric analysis substantiated quantitative estimates of volumes and surface areas for endocytic vacuoles, apical tubules, lysosomes, and microvilli in control and experimental animals. The tubule cells were ultrastructurally normal 48 hours after the injection of maleate. Conclusion. Sodium maleate causes proteinuria due to a decreased tubular reabsoprtion of protein, and it demonstrates a decreased transport of protein from endocytic vacuoles to lysosomes in proximal tubule cells and a subsequent low tubular protein catabolism.