[Ultrastructural study of podocyte alterations in non proliferative glomerulopathy]

Ultrastructural changes in podocytes are an important diagnostic and prognostic marker for nephropathies. However, the biomedical understanding of detected submicroscopic changes in podocytes remains controversial.

To investigate the relationship between the ultrastructural changes of podocytes (fusion of cytopodia and denudation of the basement membrane as a result of their desquamation) with a number of clinical and laboratory indicators of kidney dysfunction in case of non-proliferative glomerulopathies (NPGP). Thirty-seven patients (23 men, 14 women) with NPGP, including 8 with focal segmental glomerulosclerosis (FSGS), 17 with membranous nephropathy (MN), and 12 with minimal change disease (MCD), were examined.

All the patients underwent standard laboratory and instrumental studies: determinations of the levels of total serum cholesterol (mmol/l), total serum protein (g/l); serum albumin (g/l); CKD-EPI glomerular filtration rate (GFR) (ml/min/1.73 m²), and daily protein loss (g/day). Light optical changes were measured; completely sclerotic and/or focally segmentally sclerotic glomeruli were taken into account. Quantitative ultrastructural stereological analysis was carried out estimating the cytopodium width (CPW) and the degree of glomerular basement membrane denudation (GBMD) (%).

NPGP cases showed the largest number of sclerotic glomeruli in FSGS, which was accompanied by the lowest level of daily proteinuria and GFR. Quantitative values of CPW were associated with the level of daily protein loss (r=0.47; p < 0.05) and serum albumin (r=-0.57; p <0.05) in patients with nephrotic syndrome. In MN, the absolute value of CPW was larger than that in the other two patient groups. A correlation analysis of CPW and GBMD values among patients with NPGP revealed a statistically insignificant negative relation between these morphometric parameters. However, when a subgroup of patients with podocytopathies (only MCD and FSGS) was identified in the study group, this relationship was found to be significant (r=-0.54; p=0.012).

The patients with NPGP exhibited a relationship between the severity of nephrotic syndrome and proteinuria/hypoalbuminemia, on the one hand, and CPW, on the other. The established negative relationship between CPW and the percentage of GBMD in the subgroup of patients with podocytopathies may be due to the early stages of podocyte injury, which are accompanied by transient GBMD.