Acute tubular necrosis (ATN) is the predominant form of acute kidney injury (AKI), and can be ischemic or nephrotoxic in origin. Ischemic ATN is a form of pre-renal AKI where the decrease in renal perfusion leads to injury and necrosis, most commonly in the PCT and medullary ascending limb.
Ischemic ATN can be precipitated by myocardial infarction or in cases of severe blood loss. Reduced blood flow to the afferent arteriole damages endothelial cells, leading to decreased NO and increased endothelin level, which in turn cause vasoconstriction and a subsequent reduction in glomerular filtration rate (GFR). Unique to ATN, ‘muddy brown’ casts appear in the urine, indicative of the necrotic epithelial cells that accumulate in the tubular lumen.
Nephrotoxic ATI occurs due to toxic substances that damage the tubular epithelial cells, with the PCT being particularly vulnerable. Causes of nephrotoxic ATI include aminoglycosides, IV contrast, and damaged muscle (crush injuries or rhabdomyolysis).
ATN progresses through three phases: initiation, maintenance, and recovery. The initiation phase lasts ~36 hrs, and is characterized by nearly normal renal function. The maintenance phase lasts 1-2 weeks following the initial injury, and is a critical stage where the signs and symptoms of AKI develop, such as oliguria and increased BUN & creatinine. The recovery phase is marked by tubular re-epithelialization, significant diuresis (3-5L/day) and can result in electrolyte imbalances like hypokalemia, hyponatremia, hypocalcemia, & hypomagnesemia.
Acute tubular necrosis (ATN) is the predominant form of AKI and is commonly precipitated by decreased renal perfusion, termed prerenal AKI. Factors such as severe blood loss or myocardial infarction can lead to systemic hypoperfusion. This results in ischemic damage to renal tubules, culminating in ATN.
Ischemia inflicts damage on endothelial cells, leading to a decline in nitric oxide production, a vasodilator, and an increase in endothelin, a vasoconstrictor. The ischemic damage to the afferent arteriole induces vasoconstriction and hampers blood flow to the glomerulus, thereby reducing the glomerular filtration rate (GFR), a key event in the onset of ATN.
ATN manifests as "muddy brown" casts in urine sediment, a result of sloughed tubular cells. These cells can obstruct the tubular lumen, exacerbating the reduction in GFR. Histologically, the nephron in ATN will display dilated tubules, patchy loss of epithelial cells, ruptured basement membranes, and epithelial cell vacuolization.
ATN evolves through several phases: initiation, maintenance, and recovery. The initiation phase, lasting ~36 hours, is marked by the initial insult such as MI or sepsis but features relatively normal renal function and urine output. This is followed by the maintenance phase, which lasts 1-2 weeks post-insult and is characterized by AKI symptoms like oliguria and metabolic abnormalities. The recovery phase ensues, characterized by tubular re-epithelialization and profound diuresis, which may result in electrolyte imbalances.
Nephrotoxic substances can precipitate ATN, particularly the proximal convoluted tubule, which is especially susceptible. Agents such as aminoglycosides, intravenous contrast, and heme pigments from damaged muscle (as in crush injuries or rhabdomyolysis) can result to nephrotoxic ATN.