EPAS1 and renal fibrosis: In the current study, the timing of HIF-2α activation was a prime determinant of the phenotypic changes in the kidneys; renal fibrosis was aggravated when HIF-2α was activated from the beginning of CKD, while it was ameliorated via an improvement in renal hypoxia when HIF-2α was activated at a later stage of CKD.