Kidney nontumor
Tubular and interstitial diseases
Acute tubular necrosis (ATN)

Author: Nikhil Sangle, M.D. (see Authors page)

Revised: 21 March 2018, last major update December 2012

Copyright: (c) 2003-2018, PathologyOutlines.com, Inc.

PubMed Search: Acute tubular necrosis [title]

Cite this page: Sangle, N. Acute tubular necrosis (ATN). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/kidneyatn.html. Accessed May 26th, 2018.
Definition / general
  • Reversible destruction of tubular epithelial cells with acute suppression of renal function
  • Most common cause of acute renal failure
Etiology
  • Tubules are sensitive to injury due to vast electrically charged surface for reabsorption, active transport for ions and organic acids and the ability to concentrate
  • Ischemic: also called acute vasomotor nephropathy; due to inadequate renal blood flow, often from marked hypotension and shock (acute pancreatitis, severe trauma); ischemia causes vasoconstriction, which leads to reduced glomerular filtration rate and oliguria
  • Nephrotoxic: due to carbon tetrachloride, cisplatin, ethylene glycol, gentamycin, hemoglobin (transfusion reaction, malaria), lead, light chains (myeloma), mercury (Arch Pathol Lab Med 1991;115:56), methotrexate, myoglobin (from crush injury, myositis, muscle toxins), radiographic contrast agents; greatest injury is to proximal convoluted tubules
Clinical features
    Phases:
  • Initiating: 0 - 36 hours, decreased urine output, elevated BUN and creatinine due to decreased blood flow
  • Maintenance: 40 - 400 ml/day of urine, salt / water overload, hyperkalemia, acidosis and uremia; may need dialysis
  • Recovery: increased urine volume up to 3 liters/day due to tubular damage, inability to concentrate and hypokalemia; vulnerable to infection
  • Mortality: 5% if no damage to other organs, 50% if shock / sepsis

  • Non-oliguric acute tubular necrosis: increased or normal urine volumes, often associated with nephrotoxins and a more benign clinical course
  • Urinalysis: shows epithelial and granular casts
Microscopic (histologic) description
    Ischemic ATN:
  • Early: varies from cell swelling to focal tubular epithelial necrosis and apoptosis with desquamation of cells into lumen; dilated proximal tubules with thinning or loss of PAS+ brush border; hyaline, granular and pigmented cases, particularly in distal and collecting ducts, eosinophilic hyaline casts of Tamm-Horsfall protein (urinary glycoprotein normally secreted by these cells); white blood cells in dilated vasa recta, interstitial edema
  • Later: epithelial regeneration (flattened epithelium, dilated tubular lumina, large nuclei with prominent nucleoli and mitotic activity)

    Nephrotoxic ATN:
  • Extensive necrosis of tubular cells along proximal tubule

  • Carbon tetrachloride: neutral lipid accumulation / fatty change in injured cells, followed by necrosis
  • Ethylene glycol: ballooning and hydropic changes of proximal tubules, calcium oxalate crystals in tubular lumina
  • Hemoglobin / myoglobin: numerous deeply pigmented, red-brown casts in distal and collecting ducts
  • Indinavir: intraluminal clear crystals with mononuclear reaction (Kidney Int 2009;75:428)
  • Lead: dark intranuclear inclusions and necrosis
  • Mercury: large acidophilic inclusions
  • Tenofovir:distinctive proximal tubular eosinophilic inclusions representing giant mitochondria (Kidney Int 2010;78:1171)
  • Vancomycin: acute interstitial nephritis with lymphocytic and eosinophilic infiltrate and ATN (Clin Exp Nephrol 2012;16:320)
Microscopic (histologic) images

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Necrosis and sloughing of epithelial cells

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Calcium oxalate crystals (various causes)

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Denge fever: necrotic debris in tubular lumina (PAS)

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Ethylene glycol poisoning


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Indinavir toxicity

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Tenofovir toxicity

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Vancomycin toxicity

Differential diagnosis