2.2.6. Ferroptosis

The process of ferroptosis may be important in the progression of CKD [58]. Ferroptosis is a form of regulated cell death driven by iron-dependent phospholipid peroxidation and oxidative stress. With CKD, iron accumulates in renal tubular cells. If lipid peroxide repair capacity by the phospholipid hydroperoxidase, glutathione peroxidase 4 (GPX4), is lost in the presence of this iron, ferroptosis may ensue. If the uptake of cystine via the cystine/glutamate antiporter, system xc <sup>−</sup> is lost, or glutathione synthesis is otherwise impaired in the presence of this iron, ferroptosis may occur. In animal models of CKD, an iron-restricted diet exerts a renal protective effect by inhibiting oxidative stress and aldosterone receptor signaling [58].

**Figure 2.** Process of carbamylation. Carbamylation occurs through two primary pathways that converge due to the spontaneous reactivity of isocyanate with lysine residues and the N-termini of nascent polypeptides. The first and predominant pathway is the spontaneous dissociation of urea to cyanate and ammonia. The second pathway is the conversion of thiocyanate and hydrogen peroxide to cyanate under the action of myeloperoxidase. Once cyanate is formed, it is converted into isocyanate, and the spontaneous and irreversible process of carbamylation commences. MPO, myeloperoxidase.
