As a key transcription factor, hypoxia inducible factor-1 (HIF-1) induces VEGF production to protect against hypoxic renal injury in the acute hypoxia phase of the ischemic AKI model.127 Preischemic targeting of HIF prolyl hydroxylation attenuates AKI and prevents AKI-CKD progression.128 However, HIF-1-induced overproduction of several growth factors (such as VEGF and connective tissue growth factor (CTGF)) contribute to renal fibrosis in chronic hypoxia conditions.129,130 Thus, the disease condition might be critical when HIF-1/VEGF-targeted therapy is applied. The gene discussed is CCN2; the disease is renal fibrosis.