2.1.2. Capillary Network

Peritubular capillary rarefaction (loss of capillary density) is a common feature of CKD. Interestingly, capillary rarefaction correlates strongly with CKD and has been used as a predictor of progression. Loss of peritubular capillaries is strongly associated with hypoxia and interstitial fibrosis, which lead to renal functional decline [24–26]. Alterations in the expression of endothelial cell-derived factors such as VEGF-A, angiopoietin, and thrombospondin-1 lead to an imbalance of proangiogenic and antiangiogenic factors. Thrombospondin-1 is reported to inhibit renal tubular epithelial cell proliferation, due to reperfusion injury, via the CD47 receptor [27]. Furthermore, inflammatory cytokines such as interleukin (IL)-1α and tumor necrosis factor-α (TNF-α) are secreted and block VEGF-A expression, a major proangiogenic factor [28]. It has been reported that small arterial changes might be crucial primary contributors to the development of glomerulosclerosis due to the decreased number of pericapillary pericytes, as pericytes are crucial for peritubular vessel function and capillary survival [29,30]. Thus, the alteration or disequilibrium of nitric oxide, endothelin-1, endostatin, throbospondin-1, and VEGF might be causative for a functional disruption in capillaries, leading to chronic hypoperfusion, ischemia, and nephron loss.
