Acute tubular necrosis

Kidney nontumor

Tubulointerstitial disease

Ischemic injury

Author: Nikhil Sangle, M.D.

Topic Completed: 26 November 2018

Minor changes: 30 June 2020

Copyright: 2003-2021, PathologyOutlines.com, Inc.

PubMed Search: Acute tubular necrosis [title]

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Table of Contents

Cite this page: Sangle N. Acute tubular necrosis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneyatn.html. Accessed January 20th, 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

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)