From AKI to CKD: Maladaptive Repair and the Underlying Mechanisms

Abstract

Acute kidney injury (AKI) is defined as a pathological condition in which the glomerular filtration rate decreases rapidly over a short period of time, resulting in changes in the physiological function and tissue structure of the kidney. An increasing amount of evidence indicates that there is an inseparable relationship between acute kidney injury and chronic kidney disease (CKD). With the progress in research in this area, researchers have found that the recovery of AKI may also result in the occurrence of CKD due to its own maladaptation and other potential mechanisms, which involve endothelial cell injury, inflammatory reactions, progression to fibrosis and other pathways that promote the progress of the disease. Based on these findings, this review summarizes the occurrence and potential mechanisms of maladaptive repair in the progression of AKI to CKD and explores possible treatment strategies in this process so as to provide a reference for the inhibition of the progression of AKI to CKD.

Keywords: AKI; CKD; fibrosis; maladaptive repair; renal tubular epithelial cells.

Figure 1

The regulation of hypoxia-inducible factor HIF. In normoxic condition, HIF-1α is hydroxylated by prolyl hydroxylase (PHD), and then hydroxylated HIF-1α can combine with ubiquitin. This compound results in poly-ubiquitination and proteasomal degradation. However, under hypoxia environment, the hydroxylation and hydrolysis of HIF-1α are inhibited, and it binds to HIF-1β to form the HIF-1α/HIF-1β complex in the nucleus, activating the specific gene transcription.

Figure 2

Schematic diagram of pathophysiology and related biochemical pathways in the progression of AKI to CKD.