Acute Tubular Necrosis
Douglas Stahura D.O.
Grandview Hospital
7/24/2002
Causes of Acute Renal Failure
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Pre-renal
Renal parenchymal (intrinsic)
Post-renal
Acute Tubular Necrosis (ATN)
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Pre-renal azotemia and ATN are a spectrum
of manifestation of renal hypoperfusion
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Pre-renal – mild to moderate ischemia
ATN – severe/prolonged ischemia with injury to
parenchyma which does not resolve immediately
with restoration of renal perfusion
Describes the renal parenchymal injury
following renal ischemia OR exposure to
nephrotoxins, which particularly injure the
tubular epithelium
Acute Tubular Necrosis (ATN)
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What segments of the nephron? Why?
How to recognize – clinical/histological
Pathophysiology
Ischemia/toxins
Clinical course
Acute Tubular Necrosis (ATN)
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Site of tubular injury
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Proximal tubule (S3, pars recta)
Medullary thick ascending limb
Medulla receives 20% of total renal blood
flow
Intense metabolic activity
O2 supply/demand balance is delicate
Multiple causes of cell injury
Acute Tubular Necrosis (ATN)
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Causes of cell injury
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Endothelin/Nitric Oxide balance
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Endothelin(ET-1 isoform) potent vasoconstrictor
produced in renal endothelium, epithelium,
mesangium
Nitric Oxide potent vasodilator produced in
endothelium
ATP Depletion
Cell Swelling
Acute Tubular Necrosis (ATN)
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Causes of cell injury
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Intracellular Calcium increases
Intracellular acidosis
Oxidant injury
Inflammatory response from
ischemia/reperfusion
Acute Tubular Necrosis (ATN)
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Tubular Injury
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Cell swelling, vacuolation, apical blebbing,
loss of brush border, loss of cell polarity,
necrosis, sloughing
Acute Tubular Necrosis (ATN)
Histopathology
Acute Tubular Necrosis (ATN)
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Nephrotoxins
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Endogenous – myoglobin, hemoglobin,
light chains, Crystals, Hypercalcemia
Exogenous – ethylene glycol, IV contrast,
Medications: Aminoglycosides, Acyclovir,
Methotrexate, Amphotericin B, Cisplatin,
Ifosfamide, Foscarnet
Acute Tubular Necrosis (ATN)
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Clinical Course
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Initiation phase
Maintenance phase
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GFR = 5-10 ml/min
Lasts weeks to months
Recovery phase
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Heralded by increase of urine output
Acute Tubular Necrosis (ATN)
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Diagnostics
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FENA >1%
Una > 40 Meq/dL
Uosm < 350 mosm/dL
Renal Ultrasound – normal size
Urine microscopic – “muddy brown cast”
Acute Tubular Necrosis (ATN)
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Outcomes
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Mortality about 50%
Acute Tubular Necrosis (ATN)
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Treatment
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Supportive – maintain pt non-oliguric for
ease in fluid balance/management
Maintain perfusion of kidneys MAP=65
Treat underlying illness/interrupt insult
Acute Tubular Necrosis (ATN)
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Review
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Caused by severe hypoperfusion/toxin
Parenchymal injury that is not immediately
reversible
Effects the proximal and mTAL epithilium
Hallmark “muddy brown casts”
No specific treatment/remedy
Mortality 50%
References
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The Kidney 6th Edition, Brenner and
Rector
Comprehensive Clinical Nephrology,
Johnson
Clinical Physiology of Acid-Base and
Electrolyte Disorders, Rose