Grant: Operating Grant

The kidneys filter plasma at the level of the glomerulus,where the first step of urine formation occurs. Normally the glomerular filtration barrier prevents the loss of plasma proteins into the urine. In nephrotic syndrome, there is a defect in the glomerular filtration barrier and this leads to protein leakage across the barrier with subsequent edema (swelling of body with water). Congenital nephrotic syndrome has an early onset within the first 3 months of life and is treated by removing the kidneys to stop the protein loss: this then leads to a need for dialysis and future transplantation. We have identified a new gene (called RhoGDIalpha) to cause hereditary nephrotic syndrome. We propose to perform studies to understand how this mutation in RhoGDIalpha leads to a specific defect in the glomerular filtration barrier. We will further extend our findings into non-hereditary forms of nephrotic syndrome and will study the role of this protein in common causes of nephrotic syndrome in childhood.