Cellular basis of erythropoietin deficiency in renal failure. In the normal kidney, EPCs are recruited from peritubular interstitial fibroblast-like cells and pericytes. Tubular epithelial cells do not produce EPO. Under conditions of injury, EPCs or interstitial cells with EPC potential transdifferentiate into myofibroblasts, which synthesize collagen and lose their ability to produce EPO. In CKD, EPC recruitment is impaired, resulting in reduced renal EPO output and the development of anaemia. Under conditions of severe hypoxia or in patients with advanced CKD, the liver contributes to plasma EPO levels. Abbreviations: CKD, chronic kidney disease; EPC, erythropoietin-producing cell; EPO, erythropoietin.