Idiopathic focal segmental glomerulosclerosis (iFSGS) is a common cause of chronic kidney disease in children and adults that in many individuals requires renal replacement therapy (RRT). The underlying cause and pathophysiology of this disease remains poorly understood. Previously, our group has published microarray data from whole kidney biopsy tissue and found that a variety of genes are over-expressed in iFSGS (Schwab et al, 2004). More recently, we have used laser capture microdissection to look at gene expression profiles specifically in the glomerulus of patients with iFSGS (preliminary data). The role of the tubular cells in iFSGS pathogenesis has been historically overlooked until recently. In this project, I would like to better define the role of tubules, specifically proximal tubules, in addition to glomeruli in iFSGS using microarray. To obtain specific portions of the nephron, I will utilize laser capture microdissection of discarded de-identified kidney biopsy specimens previously obtained for diagnostic purposes. As an additional outcome, we will also examine kidney tissue obtained from patients with minimal change disease for comparison. To validate the microarray findings, human biopsy tissue will be processed for immunohistochemistry and some preliminary validation studies (CD24 and chemokine-1) which confirm our microarray results are presented. The goals of this study are to obtain gene profiles from glomeruli and proximal tubules in iFSGS patients and correlate this to clinical data (proteinuria, hypertension, and degree of renal failure). We hypothesize that a particular clinical phenotype will correspond with particular pattern of gene expression. The NIDDK through the Renal Genetics and Genomics program recognizes the need to understand the pathogenesis of chronic kidney diseases, like iFSGS, at the gene level. Our goal in this research project is to use microarray to screen for genes that are important in iFSGS pathogenesis and provide a guide for future basic science study. In addition, we have a long-term translational research goal of using gene expression profiles at the time of diagnosis in all iFSGS patients which will guide us along a treatment algorithm that will maximize the functional outcome. Lay summary: To better understand Focal segmental glomerulosclerosis (FSGS), a common type of kidney disease in adults and children, this project uses discarded frozen human kidney tissue and looks at genes expressed in kidney cells that leads to their inability to function normally. In this study, we screen human kidney cells for 25,000 possible genes using a technology called microarray. By generating more knowledge on the basic understanding of this disease at the gene level, we hope to develop better treatments for FSGS and clinical outcome. ? ? ?
