Table of Contents
Definition / general | Etiology | Clinical features | Microscopic (histologic) description | Microscopic (histologic) images | Differential diagnosisCite this page: Sangle N. Acute tubular necrosis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneyatn.html. Accessed February 27th, 2021.
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
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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
Microscopic (histologic) 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)
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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
Differential diagnosis
- 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