Laser microdissection and mass spectrometry shows loss of podocyte proteins in minimal change disease and focal segmental glomerulosclerosis.

Minimal change disease and primary focal segmental glomerulosclerosis (FSGS) are common causes of nephrotic syndrome. Both diseases present with massive proteinuria and widespread foot process effacement on electron microscopy examination. On the other hand, secondary FSGS can also present with significant proteinuria, although the extent of foot process effacement can be variable. In this study, we performed laser microdissection of glomeruli followed by mass spectrometry to study podocyte proteins and compare the differences between the 3 diseases. Our study shows significant decrease in total spectral counts of nephrin, podocin, CD2-associated protein, alpha actinin 4, inverted formin 2 and dystroglycan 1 in all 3 diseases compared to time zero kidney transplant controls and membranous nephropathy biopsies (p <0.001). On the other hand, the decrease in the podocyte proteins in minimal change disease, primary FSGS and secondary FSGS was comparable and there was no significant difference. Surprisingly, there was no significant decrease in the podocyte proteins in membranous nephropathy compared to time zero kidney transplant control biopsies. In conclusion, our study shows significant decrease in major podocyte proteins in minimal change disease, primary and secondary FSGS, but not in time zero kidney transplant controls and in membranous nephropathy.