Pathophysiology review: Acute tubular necrosis

April 2010 
Volume 40  Number 4
Pages 46 - 47
  PDF Version Available!

ACUTE TUBULAR NECROSIS (ATN), the most common cause of intrinsic renal failure, is characterized by destruction of tubular epithelial cells and acute suppression of renal function. Various conditions can cause ATN, including acute tubular damage from ischemia, exposure to nephrotoxic drugs or chemicals, tubular obstruction, and toxins from massive infection.Although morbidity and mortality are high in ATN, tubular injury frequently is reversible, depending on whether necrotic cells and intratubular casts are removed and renal cells regenerate. Severe ischemia that causes cortical necrosis, however, leads to irreversible renal failure.Ischemic ATN occurs most often in patients who've had major surgery, severe hypovolemia, overwhelming sepsis, trauma, or burns.1 Sepsis produces ischemia by provoking a combination of systemic vasodilation and intrarenal hypoperfusion. Toxins generated in sepsis sensitize renal tubular cells to the damaging effects of ischemia. In trauma and burn patients, ATN has many contributing causes, including hypovolemia and the myoglobin and toxins released by damaged tissue. Glomerular filtration rate (GFR) doesn't improve after renal perfusion is restored, as it would with prerenal failure.Nephrotoxic ATN causes renal injury by varying combinations of renal vasoconstriction, direct tubular damage, and intratubular obstruction. Because of its rich blood supply and ability to concentrate toxins to high levels, the kidney is particularly vulnerable to toxic injury. Adding to the danger, the kidney metabolizes relatively harmless agents into toxic metabolites. Drugs that are directly toxic to renal tubules include antimicrobials such as aminoglycosides, chemotherapeutic drugs such as cisplatin and ifosfamide, and radiocontrast agents used during cardiac catheterization and other diagnostic imaging.2,3Contrast nephrotoxicity is thought to result from direct tubular toxicity and renal ischemia.4 The risk of renal damage from contrast medium

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