Acute Tubular Necrosis

Overview
  • Acute Tubular Necrosis (ATN) refers to a characteristic pathologic change in the renal interstitium. Although two basic pathogenic mechanisms can lead to ATN, referred to as Ischemic ATN and Nephrotoxic ATN, a common set of morphological changes and clinical consequences result.
Ischemic ATN
  • Overview
    • Ischemic ATN is fundamentally caused by reduced perfusion of the renal interstitium, resulting in ischemia to this tissue. The tubular epithelium is highly prone to ischemic injury for two basic reasons. First, the tubular epithelium is highly metabolically active in certain segments where substantial amounts of resorption and secretion occur. Second, the renal medulla has a relatively low oxygen saturation at baseline given the fact that it receives all of its perfusion from the vasa recta which, due to their geometry and the fact that they lie after the glomerulus, carry very little oxygen to the medulla. Consequently, Ischemic ATN generally affects metabolically active segments of the tubule which lie near the renal medulla (i.e. terminal proximal tubule and thick ascending loop of Henle).
  • Pathogenic Consequences
    • Ischemia of the tubule results in ischemic necrosis of tubular epithelial cells and deranges their functionality. Some of these functional derangements may be due to the disruption of tight junctions between epithelial cells, allowing the NaK ATPase to migrate to a luminal location and thus pumping sodium back into the lumen. Increased distal sodium delivery then activates tubuloglomerular feedback which induces afferent arteriolar vasoconstriction, thus aggravating medullary ischemia.
  • Etiologies
    • Ischemic ATN generally results from situations that cause sudden systemic hypotension that in turn reduce perfusion of kidneys. This commonly occurs during the context of surgeries, shock or hypovolemia, although any etiology causing sudden hypotension can be a culprit. In this sense, Ischemic ATN, which is a subtype of intrinsic acute renal failure, can be thought of as a complication of extreme prerenal acute renal failure.
Nephrotoxic ATN
  • Overview
    • Nephrotoxic ATN occurs in response to the presence of several exogenous or endogenous toxins which are freely filtered across the glomerular basement membrane. The pathogenic mechanism by which these toxins cause ATN is probably diverse.
  • Etiologies
    • Radiocontrast Agents: Likely the most common cause of ATN in hospitalized patients after CT scans
    • Antiobiotics: Aminoglycosides, Amphotericin B, among others
    • Chemotherapeutics: Cisplatin, among others
    • Chemicals: Mercuric Chloride, ethylene glycol
    • Heme: Initiation of ATN by heme requires high concentrations that can occur during hemolysis or rhabdomyolysis
Morphology
  • Overview
    • Regardless of the pathogenesis, ATN is characterized by a common set of morphological changes. These morphologic changes usually appear in a segmental pattern with some segments of the nephron, such as the proximal tubule and thick ascending loop of Henle, more susceptible than others.
  • Tubular Epithelium
    • The tubular epithelium undergoes necrosis which can be seen by denudation of tubular epithelial cells. In some cases the tubular basement membrane may rupture.
  • Tubular Lumen
    • The denuded and necrotic tubular epithelial cells ultimately fall into the tubular lumen and often plug the tubule in the form of proteinacious casts. When ATN is initiated by hemolysis or rhabdomyolysis, heme pigment may be precipitated in the luminal debris.
Clinical Consequences
  • ATN is the most common cause of acute renal failure, defined as a sudden drop in GFR yielding a variety of symptomology such as oliguria (See: Acute Renal Failure). Because the pathology of ATN is centered around the renal interstitium, ATN-induced renal failure is considered to be a subtype of Intrinsic ARF. The mechanism by which GFR is reduced in ATN is not well-understood, but plugging of the tubular lumen by cellular debris combined with backleak of solutes across the injured tubular epithelium probably contribute. However, ATN is highly reversible and if the underlying source of injury (i.e. renal ischemia or presence of toxin) is corrected, the tubular epithelium rapidly recovers and renal function is restored.