Ultrastructural podocyte alterations and autophagosome number in pediatric podocytopathies: associations with CD36 and NLRP3 expression.

INTRODUCTION: Focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) are pediatric podocytopathies characterized by podocyte injury and nephrotic syndrome. Podocyte structural integrity depends on tightly regulated mechanisms of cellular homeostasis, including autophagy. However, ultrastructural alterations associated with pediatric podocytopathies remain incompletely characterized. We investigated podocyte ultrastructural alterations, autophagosome number, and glomerular CD36/NLRP3 expression in pediatric podocytopathies. METHODS: This retrospective cross-sectional study evaluated renal biopsies from 37 children diagnosed with FSGS (n = 16) or MCD (n = 21). Glomerular CD36 and NLRP3 expression were assessed by immunohistochemistry, whereas foot process width and autophagosome number were evaluated by transmission electron microscopy. RESULTS: Both FSGS and MCD showed increased foot process width and reduced autophagosome number compared with controls. Autophagosome number correlated negatively with foot process width in both groups. CD36 expression was reduced in MCD compared with controls and FSGS, whereas NLRP3 expression was increased in FSGS compared with controls. In MCD, NLRP3 expression correlated positively with CD36 expression and autophagosome number. CONCLUSION: Pediatric FSGS and MCD exhibited distinct patterns of podocyte ultrastructural alterations accompanied by differences in glomerular CD36/NLRP3 expression. These observations suggest heterogeneous alterations in cellular homeostasis between pediatric podocytopathies and warrant further investigation into mechanisms associated with podocyte structural integrity and injury.