What stimulates the release of erythropoietin by the kidneys?

Hypoxia: This is a very complex process. The simplest answer is: hypoxia (low oxygen tension, anemia) stimulates HIF production (hopoxia-inducible factor) which then stimulates EPO release from the kidney. Another protein called VHL inhibits HIF action on EPO (negative regulator). Mutation of VHL can cause excessive EPO release, resulting in congenital erythrocytosis (a rare genetic disorder).