Source and microenvironmental regulation of erythropoietin in the kidney.

Purpose of reviewHistorically, the identity of O-2-sensing renal erythropoietin (Epo)-producing (REP) cells was a matter of debate. This review summarizes how recent breakthroughs in transgenic mouse and in-situ hybridization techniques have facilitated sensitive and specific detection of REP cells and accelerated advancements in the understanding of the regulation of renal Epo production in health and disease.Recent findingsREP cells are a dynamically regulated unique subpopulation of tubulointerstitial cells with features of fibroblasts, pericytes and neurons. Under normal conditions, REP cells are located in the corticomedullary border region within a steep decrement in O-2 availability. During the progression of chronic kidney disease (CKD), REP cells cease Epo production, dedifferentiate and contribute to the progression of renal fibrosis. However, CKD patients with renal anaemia still respond with elevated Epo production following treatment with hypoxia-mimicking agents.SummaryWe hypothesize that REP cells are neuron-like setpoint providers and controllers, which integrate information about blood O-2 concentration and local O-2 consumption via tissue pO(2), and combine these inputs with intrinsic negative feedback loops and perhaps tubular cross-talk, converging in Epo regulation.