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Kidney non-tumor

Tubular and interstitial diseases

Acute tubular necrosis (ATN)


Reviewers: Nikhil Sangle, M.D. (see Reviewers page)
Revised: 24 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
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● Reversible destruction of tubular epithelial cells with acute suppression of renal function
● Most common cause of acute renal failure

Etiology
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● 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
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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

Micro description
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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)

Micro images
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Necrosis and sloughing of epithelial cells


Calcium oxalate crystals (various causes)


Denge fever: necrotic debris in tubular lumina (PAS)


Ethylene glycol poisoning


Indinavir toxicity


Post-transplant (24 hours): isografts and allografts (A and B)


Post-transplant (1 week): human cadaveric kidney


Tenofovir toxicity


Vancomycin toxicity

Virtual slides
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ATN: due to ethylene glycol poisoning, cause unspecified

Electron microscopy images
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Granulocytes and mononuclear cells aggregating in a peritubular capillary


Tenofovir toxicity

Differential diagnosis
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● Other causes of acute renal failure (urine output < 400 ml/24 hr): hemolytic-uremic syndrome, malignant hypertension, polyarteritis nodosa
Acute tubulointerstitial nephritis: severe interstitial inflammation and associated tubulitis
● DIC
Pyelonephritis with papillary necrosis
Rapidly progressive glomerulonephritis
● Urinary obstruction

End of Kidney non-tumor > Tubular and interstitial diseases > Acute tubular necrosis (ATN)

Ref Updated: 8/16/12


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