Role of hypoxia in progressive chronic kidney disease and implications for therapy

Abstract

Chronic hypoxia in the tubulointerstitium has been recognized as a final common pathway that leads to the development of end-stage renal disease. Hypoxia-inducible factor (HIF), a master regulator of the adaptive response against hypoxia, is involved in the pathogenesis of chronic kidney disease (CKD). This review focuses on HIF and novel therapeutic strategies targeting HIF. Although HIF upregulation is beneficial against hypoxic kidney injury, it may be harmful under certain pathological conditions. Recent advances in epigenetic changes provide an additional layer of complexity to our understanding of gene regulation in response to hypoxia, which is most likely involved in the progression of CKD. On the basis of this novel knowledge, the pharmacological activation and modulation of HIF is emerging as a novel therapeutic target. HIF plays a crucial role in the pathophysiology of CKD. The underlying molecular mechanisms, including epigenetics, have been thoroughly investigated. On the basis of the experimental data available to date, the pharmacological activation of HIF is likely a novel promising therapy for CKD.