Mechanisms of maladaptive repair after AKI leading to accelerated kidney ageing and CKD

Abstract

Acute injury to the kidney is often associated with maladaptive repair and incomplete resolution, leading to residual abnormalities in kidney structure and function Increasing age, and chronic low-grade insults to the tubular epithelium increase epithelial cell sensitivity to episodes of acute kidney injury, leading to maladaptive repair and progression of chronic kidney disease Maladaptive repair is characterized by fibrosis, vascular rarefaction, tubular loss, glomerulosclerosis and the presence of a chronic inflammatory infiltrate within the kidney Injured renal tubular epithelial cells become arrested at G2/M and adopt a profibrotic phenotype, which affects other epithelial cells, pericytes and the immune system Myofibroblasts that likely arise from renal pericytes proliferate and contribute to the deposition of extracellular matrix and resulting fibrosis within the injured kidney Maladaptive repair after acute kidney insults shares many common features with kidney ageing and can be thought of as a state of accelerated kidney ageing