| Acute tubular necrosis | |
|---|---|
| Specialty | Nephrology |
Acute tubular necrosis (ATN) is a medical condition involving thedeath of tubularepithelialcells that form therenal tubules of thekidneys. Because necrosis is often not present, the termacute tubular injury (ATI) is preferred by pathologists over the older name acute tubular necrosis (ATN).[1] ATN presents withacute kidney injury (AKI) and is one of the most common causes of AKI.[2] Common causes of ATN includelow blood pressure and use ofnephrotoxic drugs.[2] The presence of "muddy browncasts" of epithelial cells found in the urine duringurinalysis ispathognomonic for ATN.[3] Management relies on aggressive treatment of the factors that precipitated ATN (e.g.hydration and cessation of the offending drug). Because the tubular cells continually replace themselves, the overallprognosis for ATN is quite good if the underlying cause is corrected, and recovery is likely within 7 to 21 days.[2]
ATN may be classified as eithertoxic orischemic. Toxic ATN occurs when the tubular cells are exposed to a toxic substance (nephrotoxic ATN). Ischemic ATN occurs when the tubular cells do not get enough oxygen, a condition that they are highly sensitive and susceptible to, due to their very highmetabolism.[4] Due to several reasons, the proximal portion of the renal tubule is most commonly injured in ATN.
Acute tubular necrosis is classified as a "renal" (i.e. not pre-renal or post-renal) cause of acute kidney injury. Diagnosis is made by a FENa (fractional excretion of sodium) > 3% and presence of muddy casts (a type ofgranular cast) in urinalysis. On histopathology, there is usuallytubulorrhexis, that is, localized necrosis of the epithelial lining in renal tubules, with focal rupture or loss of basement membrane.[5] Proximal tubule cells can shed with variable viability and not be purely "necrotic".[6][7][8][9][10]
Toxic ATN can be caused by freehemoglobin ormyoglobin, by medication includingantibiotics such asaminoglycoside,[11]statins such asatorvastatin,bisphosphonates likepamidronate[12] andcytotoxic drugs such ascisplatin, or by intoxication (ethylene glycol, "anti-freeze").
Histopathology: Toxic ATN is characterized by proximal tubular epithelium necrosis (no nuclei, intense eosinophilic homogeneous cytoplasm, but preserved shape) due to a toxic substance (poisons, organic solvents, drugs,heavy metals). Necrotic cells fall into the tubulelumen, obturating it, and determining acute kidney failure. Basement membrane is intact,[citation needed] so the tubular epithelium regeneration is possible.Glomeruli are not affected.[2]
Ischemic ATN can be caused when thekidneys are not sufficiently perfused for a long period of time (i.e.renal artery stenosis) or duringshock.Hypoperfusion can also be caused byembolism of the renal arteries. Given their importance in massive nutrient and electrolyte reabsorption, the proximal tubule and medullary thick ascending limb require significant ATP and are most susceptible to ischemic damage. Thus, ischemic ATN specifically causesskip lesions through the tubules.[3]
Ischemic ATN often involvesreperfusion injury to the kidney. When oxygen flow is restored, damage can occur due tooxygen radicals, inflammatory cells and molecules and tissue edema. These processes can exacerbate injury and worsen theprognosis. Nevertheless, restoring blood flow is essential for tissue survival, so clinical strategies aim to minimize the harmful effects.[13]