In this context, the activation of hypoxic signaling in renal tissues of Sirt3-deficient mice was accompanied by a parallel increase, even prior to ADR-induced damage, in the expression of Angiopoietin-2 (Angpt-2), a multimeric protein involved in vascular remodeling, which was found to be induced in mice with CKD in injured tubular cells [35] and also in renal tubular and endothelial cells of mice with AKI [36]. Here, SIRT3 is linked to chronic kidney disease.