The HIF System Response to ESA Therapy in CKD‐Anemia

Abstract

Anemia is a common complication of chronic kidney disease (CKD) associated with disease progression and increased mortality. This anemia is mainly due to inadequate production of erythropoietin (EPO) by the failing kidneys, resulting from the reduction in renal EPO-producing cells (REPC) or from dysregulation of the hypoxia-inducible factor (HIF) system that regulates several genes related to hypoxia, angiogenesis, fibrosis and glucose metabolism, among others. In this chapter, we present a review on the HIF system in CKD-anemia, the HIF response to erythropoiesis-stimulating agents (ESA) therapy and its potential involvement in the development of ESA resistance by enhancing kidney fibrosis and inflammation. Due to concerns related to ESA use, new drugs to correct anemia are under study, being the prolyl hydroxylase inhibitors the most promising candidates.

Hypoxia-Inducible Factor-1α: The Master Regulator of Endothelial Cell Senescence in Vascular Aging

“…It was also shown that the final Moreover, extensive crosstalk between HIF and two master regulators of the inflammatory response, NF-κB and the signal transducer and activator of transcription 3 (STAT3), has been reported [108,116,117]. Under hypoxic conditions, canonical NF-κB signaling activates HIF-1α through the interactions between p50 and p65 subunits and responsive elements in the promoter of the HIF-1α gene [118]. The crosstalk between HIF-1α and NF-κB signaling during senescence has been investigated in several contexts, and its role in orchestrating SASP is widely accepted in atherosclerotic plaques.…”