Glomerular epithelial cell structure and function in chronic proteinuria induced by homologous protein-load.

The pathogenesis of glomerular scarring in proteinuric diseases is unknown, but glomerular epithelial cell (GEC) injury has been implied by the glomerular pathology seen in patients with focal segmental glomerular sclerosis and the nephrotic syndrome. We studied the effect of proteinuria on glomerular histology and GEC structure and function in rats made proteinuric for up to 8 weeks by the daily parenteral injection of homologous serum albumin. Proteinuria in the albumin-injected rats peaked at a mean level of 131 +/- 12 mg/24 hours (mean +/- SD) during the 1st week. It subsequently plateaued at 41 +/- 6 mg/24 hours but remained significantly greater than the saline-injected controls throughout the study. The albumin-injected rats developed slight but significant increases in blood pressure, serum albumin, plasma volume, and urine urea nitrogen compared to the saline injected controls. The serum creatinine was not different from controls. In the albumin-injected rats no glomerular scarring was observed after 8 weeks of proteinuria. The GEC developed albumin reabsorption droplets and signs of activity including increased numbers of organelles, vacuoles, and cytoplasmic hypertrophy, but there were no signs of irreversible GEC damage. The GEC foot processes were quantitated morphometrically, and there was no evidence of effacement after eight 4 or 8 weeks of proteinuria. GEC endocytic function, evaluated by the technique of protamine heparin aggregate disappearance, was not different from the saline injected controls. Proteinuria caused by the chronic administration of homologous serum albumin for 8 weeks is regularly associated with increased blood pressure, plasma volume, and serum albumin and ultrastructural changes in the GEC. These morphologic changes in the GEC apparently represent a normal response to proteinuria and are not evidence for irreversible cell damage. Despite their avid endocytosis of filtered plasma proteins, GEC endocytic function remains normal. These experimental results imply that glomerular sclerosis is not a consequence of proteinuria per se.