Inflammation and dyslipidaemia co-exist in patients with chronic kidney disease. This project examines how these two factors may interact to contribute to progression of kidney injury and the premature development of arterial disease. Our results show that inflammatory cytokines disrupt intracellular lipid metabolism thereby causing intracellular lipid accumulation (foam cell formation). This is the result of both excess lipid uptake and impaired lipid export from the cell. On-going work is investigating the mechanisms by which a cell is able to "sense" its intracellular lipid cholesterol level and respond accordingly, a process that involves sterol regulatory element binding protein (SREBP) cleavage activating protein (SCAP). Importantly, pharmaceutical compounds that stimulate peroxisome proliferator activator receptors (PPARs) appear to protect against intracellular lipid accumulation. Dr Zac Varghese is also involved in studying the involvement of lipids in chronic allograft nephropathy and the anti-inflammatory and anti-atherosclerotic effects of specific immunosuppressive drugs.