The pathogenesis of acute kidney injury (AKI) depends on the underlying cause but generally involves a reduction in renal perfusion, tubular cell injury, or urinary obstruction. In prerenal AKI, the kidneys conserve sodium and water to maintain perfusion, but prolonged hypoperfusion can lead to ischemia and progression to intrinsic AKI. In cases of intrinsic renal injury, particularly in ATN, ischemic or toxic insults lead to the death of tubular cells, resulting in sloughing of dead cells into the tubular lumen, causing obstruction and back-leak of filtrate. This disrupts the kidneys' ability to filter blood, leading to a decline in GFR. Postrenal AKI, on the other hand, results from physical obstruction of the urinary tract, causing increased hydrostatic pressure and reduced filtration.
At the cellular level, AKI often involves oxidative stress, inflammation, and apoptosis. Inflammation plays a key role in AKI progression, with the activation of immune cells and the release of pro-inflammatory cytokines contributing to renal damage. Additionally, ischemia and nephrotoxins disrupt the integrity of the renal tubular epithelium, causing cell death and a loss of kidney function.
