BACKGROUND: Synaptopodin is a proline-rich protein intimately associated with actin microfilaments present in the podocytes' foot processes. We investigated for synaptopodin expression in children with idiopathic nephrotic syndrome (INS), including minimal change disease (MCD), diffuse mesangial hypercellularity (DMH), and focal segmental glomerulosclerosis (FSGS); in children with congenital nephrotic syndrome of the Finnish type (CNF); and in normal kidney tissue. In particular, we examined whether an association exists between synaptopodin expression in podocyte cells and the response to steroids in INS, and whether synaptopodin expression can predict FSGS upon the initial kidney biopsy in children who progress from MCD or DMH to FSGS.
METHODS: Immunohistochemistry was performed for synaptopodin expression on renal tissues from MCD (N = 18), DMH (N = 7), FSGS (N = 13), CNF (N = 9), and normal children (N = 7). Synaptopodin expression in nonsclerosed glomeruli was quantitated by computerized image analysis on the Optimastrade mark software for both luminance (L) and percentage of glomerular area (A).
RESULTS: Synaptopodin expression was absent in areas of sclerosis. In nonsclerosed glomeruli, synaptopodin was significantly less expressed in all groups of INS and in CNF compared with normal (P < 0.0001 for both L and A, in each MCD, DMH, FSGS, and CNF). In INS, synaptopodin expression decreased in order from MCD to DMH to FSGS, reaching statistical significance between MCD and FSGS (P = 0.001 for L and P = 0.05 for A). Greater synaptopodin expression in podocytes was associated with a significantly better response to steroid therapy (P < 0.05 for both L and A). On the other hand, the expression of synaptopodin did not predict progression of MCD or DMH to FSGS.
CONCLUSION: We conclude that measurement of synaptopodin has the potential to be used as a marker to study the alteration in podocyte cell and response to therapy in INS.
Child; Child, Preschool; Disease Progression; Glomerular Mesangium; Glomerulosclerosis, Focal Segmental; Humans; Immunohistochemistry; Kidney; Kidney Diseases; Microfilament Proteins; Nephrosis, Lipoid; Nephrotic Syndrome; Reference Values
Srivastava, T., Garola, R. E., Whiting, J. M., Alon, U. S. Synaptopodin expression in idiopathic nephrotic syndrome of childhood. Kidney international 59, 118-125 (2001).