Synaptopodin expression in idiopathic nephrotic syndrome of childhood

Background. Synaptopodin is a proline-rich protein intimately associated wi th actin microfilaments present in the podocytes' foot processes. We invest igated for synaptopodin expression in children with idiopathic nephrotic sy ndrome (INS), including minimal change disease (MCD), diffuse mesangial hyp ercellularity (DMH), and focal segmental glomerulosclerosis (FSGS); in chil dren with congenital nephrotic syndrome of the Finnish type (CNF); and in n ormal kidney tissue. In particular, we examined whether an association exis ts between synaptopodin expression in podocyte cells and the response to st eroids in INS, and whether synaptopodin expression can predict FSGS upon th e 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), a nd normal children (N = 7). Synaptopodin expression in nonsclerosed glomeru li was quantitated by computerized image analysis on the Optimas(TM) softwa re for both luminance (L) and percentage of glomerular area (A). Results. Synaptopodin expression was absent in areas of sclerosis. In nonsc lerosed glomeruli, synaptopodin was significantly less expressed in all gro ups 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 i n 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 exp ression 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 expres sion 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 respons e to therapy in INS.