However, as aforementioned, HIF-2α activation at a later stage of CKD may reverse the deleterious impact of renal hypoxia by improvement of peritubular vascular integrity, and the positive effect may overcome the induction of profibrotic and proapoptotic genes by HIF-2α in tubule cells per se (Fig. 7). The gene discussed is EPAS1; the disease is chronic kidney disease.