2.1.3. Tubular Epithelial Cells

The renal proximal tubule absorbs the majority of filtered solutes in an energyconsuming process. The reported contribution of acute kidney injury (AKI) to CKD has focused attention on the proximal tubule as the main target of injury in the progression of CKD. Cells with high energy demand and slow proliferation, such as proximal renal tubules, are predisposed to oxidative damage and consequent injury [31]. Juvenile mice with a targeted deletion of endothelial nitric oxide synthase (eNOS) display renal cell death and renal cortical scars [32]. It is reported that patients with eNOS polymorphisms have increased susceptibility to the progression of CKD and thus, eNOS has been recognized as an important survival factor [33]. Tubular cells, which have a long life and high metabolic activity, rely heavily on proper mitochondrial function [34]. Mitochondrial density remains constant in hypertrophied renal tubular cells, but mitochondrial volume increases by over 50% [35]. Increased functionality may lead to additional mitochondrial oxidative stress, resulting in mitochondrial dysfunction. This dysfunction may lead to inflammation, additional alterations in intracellular homeostasis, and additional cellular injury [31,36,37].
