The relationship between glomerular function and podocyte structure of pre-proteinuria and acute nephrosis in puromycin aminonucleoside-induced rat models: a comparative electron microscopic study

Abstract

Puromycin aminonucleoside (PA) has been generally utilized as model of podocyte injury followed by massive proteinuria, severe damage on endocytotic activity of epithelial cells and postmodification of endocytosed compounds. However, total PA nephrosis (PAN) mechanism cannot be understood. We aimed to study glomerular function, foot process degeneration and transport pathways of podocytes in pre-proteinuria and acute PAN rats. Eighteen male Wistar albino rats were divided into three groups: control, pre-proteinuria and acute nephrosis groups (n=6). PA was injected into pre-proteinuria group for three times and acute group for nine times. Proteinuria levels in urine, creatinine and albumin levels in blood were detected 24 hours after PA injections. Renal cortex samples were prepared for transmission electron microscopy. Proteinuria levels in acute group significantly elevated, whereas creatinine clearance, serum albumin levels and urine volumes diminished compared to control and pre-proteinuria groups. In pre-proteinuria group, hypertrophy and structurally rich cytoplasm were detected only within podocytes. Acute group had various protein absorption granules secreted from podocyte cytoplasm to the urinary space through exocytosis after lysosomal digestion; but not observed in pre-proteinuria group. The number of slit pores in pre-proteinuria group decreased, particularly related to fusion of foot processes, subsequently leading to proteinuria. We concluded that foot process fusion begins prior to development of proteinuria although their serum albumin and creatinine clearance levels do not differ significantly. Additionally, we suggested that in acute PAN, first affected glomerular cells could be podocytes and there could be a correlation between glomerular function and number of slit pores.