Glomerular diseases account for approximately 80 percent of end stage kidney disease (ESKD). Nearly 600,000 US residents have end-stage kidney disease (ESKD) at an annual Medicare expenditure of 28 billion dollars. Through RNA profiling in our models of FSGS, we have found that HDAC activity is increased in the glomerulus and blocking with HDAC inhibitor, valproic acid or suberanilohydroxamic acid mitigates progression of kidney disease. During the last funding period, we have generated podocyte specific knockout mice for HDAC1 and 2, which also appears protective against glomerular injury in toxin mediated and genetic mouse models. In parallel, the co-PI of this study, F. Perry Wilson has continued to examine the Veterans Affairs Cohort and added multiple other cohorts to examine the stability of preliminary results that suggested a protective role of VPA in proteinuric kidney disease.