Fig. 1

Mechanism underlying the correlation between capillary rarefaction and CKD involves the tissue hypoxia, recruitment of proinflammatory factors and reactive oxygen species (ROS), macrophages infiltration and pericyte detachment and migration. Loss of capillaries accompanied by hypoxia would induce an injury cascade with oxidative stress and inflammation. Proinflammatory cytokines induce not only increase expression of endothelial adhesion molecules but also cells present in the microenvironment, such as fibroblasts and myofibroblasts. Oxidative stress contributes to progression of kidney disease by upregulating production of ROS, which promote apoptosis and necrosis of endothelial cells. Oxidative stress and inflammation also promote endothelial-mesenchymal transition (EndMT) and epithelial-mesenchymal transition (EMT). Macrophages leak into the renal interstitium through injured endothelial cell–cell contacts and undergo macrophage-fibroblast transformation (MMT). The injured endothelial cells induced by stimulus deliver signals to pericytes, leading to the detachment of pericytes from the PTCs, migration into the interstitium, where they differentiate into myofibroblasts