PODOCYTES IN CHILDHOOD MINIMAL CHANGE NEPHROTIC SYNDROME Anne-Tiina Lahdenkari Pediatric Graduate School Hospital for Children and Adolescents and Program for Developmental and Reproductive Biology

.......................................................................................................................................8 REVIEW OF THE LITERATURE................................................................................................11 1. NORMAL GLOMERULAR FILTRATION .................................................................................11 1.1 PHYSIOLOGY .............................................................................................................................11 1.2 ANATOMY .................................................................................................................................13 1.2.1 Endothelium ......................................................................................................................13 1.2.2 Glomerular basement membrane (GBM) .........................................................................14 1.2.3 Visceral epithelium (podocytes)........................................................................................14 1.2.4 Slit diaphragm (SD) ..........................................................................................................16 1.2.5 Foot process cytoskeleton .................................................................................................19 2. PROTEINURIA .............................................................................................................................20 2.1 GBM AND PROTEINURIA ...........................................................................................................21 2.2 PODOCYTES AND PROTEINURIA .................................................................................................22 2.2.1 Foot process effacement and the filtration pores..............................................................23 2.2.4 Foot process detachment ..................................................................................................24 2.2.5 Disruption of the SD .........................................................................................................25 3. NEPHROTIC KIDNEY DISEASES IN CHILDREN...................................................................26 3.1 CONGENITAL NEPHROTIC SYNDROME OF THE FINNISH TYPE (NPHS1, CNF) ............................27 3.2 FOCAL AND SEGMENTAL GLOMERULOSCLEROSIS (FSGS) .........................................................28 3.3 MINIMAL CHANGE NEPHROTIC SYNDROME (MCNS) .................................................................29 3.3.1 Pathogenesis .....................................................................................................................30 3.3.2 Clinical features................................................................................................................30 3.3.3 Long term outcome ...........................................................................................................31 AIMS OF THE STUDY...................................................................................................................33