Accumulation of lipid in tubular epithelial cells has been proposed to have a pathogenic role in the development of renal fibrosis. New findings, however, indicate that dysfunctional fatty acid oxidation rather than intracellular lipid accumulation per se induces the development of renal fibrosis. Fibrosis is a final common pathway in various forms of chronic kidney disease (CKD). To investigate common cellular pathways involved in the development of fibrosis, Katalin Susztak and colleagues performed genome-wide transcriptome analyses of 95 microdissected human kidney samples from patients with diabetic or hypertensive CKD and from individuals with normal kidney function. Their analyses identified several metabolic pathways that were altered in the CKD samples; levels of genes related to fatty acid metabolism and glucose oxidation, in particular, were considerably lower in samples from patients with CKD than in those from healthy controls. The lower levels of fatty acid oxidation were associated with an accumulation of lipid in tubular epithelial cells. Similarly, mice with either genetically induced renal fibrosis or folic acid-induced nephropathy had lower transcript levels of key enzymes involved in fatty acid oxidation, including the transcriptional regulators