Fig. 1.

Glomerular or tubular injury initiates chronic kidney disease (CKD), but the tubulointerstitial response is primarily responsible for progression. (1) Podocyte dysfunction or depletion leads to proteinuria, causing reactive changes in the tubular cells. (2) Podocyte depletion also permits the transudation of glomerular filtrate directly into the periglomerular tubulointerstitium, depositing a number of biologically active molecules in that compartment. (3) As the number of effective nephrons decreases, the remaining nephrons hypertrophy. An increased amount of filtrate per nephron increases metabolic demand on the tubules, which under even normal circumstances have high energy requirements. Thus, further stress on tubule cell homeostasis results in activation of the cells, away from a state of relatively orderly transporter function. ROS Reactive oxygen species