Recurrent focal glomerulosclerosis in the era of genetics of podocyte proteins: theory and therapy

Abstract

Focal segmental glomerulosclerosis (FSGS) is the most frequent cause of intractable proteinuria in children and adults and is emerging as a major glomerular cause of chronic kidney disease [1]. Most of the aspects related to its pathogenesis remain unknown, one major issue being post-transplant recurrence. Recent advances in molecular genetics of FSGS led to the identification of several genes responsible for familial forms. In general, they code for proteins of the podocyte and are specifically localized in the glomerular slit-diaphragm where they play a critical role in the control of glomerular permeability. The clinical implications of one of them, that is NPHS2 coding for podocin, are obvious as it’s involvement has been extended to sporadic FSGS [2–4]. Experience with inherited sporadic FSGS due to NPHS2 mutations is accumulating and shows strong clinical homologies with idiopathic FSGS, in spite of clear pathogenic differences. This offers an invaluable opportunity for a critical reevaluation of the mechanisms, which are presently thought to be involved in the pathogenesis of idiopathic FSGS and in its recurrence after renal transplantation.