Figure 1.

Scheme of the pathophysiology of unilateral ureteral obstruction (UUO). As a response to unilateral ureteral obstruction the glomerulus increases vascular renin production along with activation of the renin-angiotensin system, which leads to stimulation of transforming growth factor-β1 (TGF-1β). The proximal tubular epithelium activates the renin-angiotensin system as well. Additionally, it increases production of reactive oxygen species (ROS), which impair mitochondrial function, as well as kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Collecting duct injury leads to downregulation of epidermal growth factor (EGF) and upregulation of peritubular mesenchymal collars that express α-smooth muscle actin (α-SMA) and L1 cell adhesion molecule (L1CAM). Injury of glomeruli, proximal tubule, and collecting duct lead to tubular cell death (apoptosis, necrosis, and necroptosis), which itself leads to atubular glomeruli and tubular atrophy. In the interstitium, there is an upregulation of chemokines (CCL-2, CCL-5) and adhesion molecules as an response to obstruction. This leads to macrophage recruitment, interstitial inflammation, and stimulation of myofibroblast proliferation, which causes fibrosis. The figure is adapted from (27).