Modulation of the different components of HPHE signaling may also be advocated using pharmacological PHD inhibitors (PHIs) to induce endogenous defense mechanisms, as described with “hypoxic preconditioning” for various causes of AKI and CKD, including TMs (reviewed in Shu et al. 2019; Tanaka 2016; Tiwari and Kapitsinou 2021); see also “General considerations” in “Impact of toxic metal ions on the renal HPHE signaling axis”). This evidence concerns the gene PDC and acute kidney injury.