Proposed pathophysiology of renal impairment in 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced chronic liver disease (CLD) model mice.

<p>DDC feeding leads to renal impairment with sublethal tubular cell injury. The tubules show: 1) the mitochondrial injuries and consequent oxidative stress with the generation of reactive oxygen species (ROS). 2) The injury is prevented from progressing to cell death through two defense mechanisms: autophagy and single-cell extrusion with regeneration. 3) The kidney remains in a state of sublethal injury with loss of brush border and mitochondrial injury (early phase). However, 4) activation and proliferation of myofibroblasts appear after long-term feeding (late phase), leading to an increased production of collagen fibers and progression to chronic kidney disease (CKD).