Glomerular derangement is the major feature of a diverse array of kidney disorders that lead to end-stage kidney disease (ESKD). Podocyte dysfunction is central to the underlying pathophysiology of many common glomerular diseases, including diabetic nephropathy (DN), focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), and genetic forms of nephrotic syndrome, and is associated with heavy proteinuria. Loss of podocyte foot process structure, or effacement, is the key feature of podocyte injury in these proteinuric glomerular disorders, also called "podocytopathies". However, the degree of effacement can vary: For instance, it is very disseminated (diffuse) in minimal change disease, but more variable (segmental) in focal segmental glomerulosclerosis. Recent work has shown that nephrin, ROBO2, and SLIT2 are proteins implicated in these podocyte foot process effacement and podocytopathy. We sought to evaluate changes in the expression of these proteins using immunofluorescence microscopy, and the degree of foot process effacement in podocytopathies using ultrastructural morphometry. In podocytopathies, we saw increased expression of ROBO2 and decreased expression of nephrin indicating that, upregulation of ROBO2 may lead to podocyte injury and podocyte injury may result in loss of nephrin. In addition, SLIT2, which binds ROBO2, was found in tubules and in glomeruli. A higher degree of geometric mean foot process width was vii observed in podocytopathies as compared to normal kidney. These findings can be used in the clinical setting to diagnose and monitor disease treatment. / 2024-02-07T00:00:00Z