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1. Acute Tubular Necrosis
DR RAI M. AMMAR MADNI

2. Causes of Acute Renal Failure
Pre-renal
Renal parenchymal (intrinsic)
Post-renal

4. Acute Tubular Necrosis (ATN)
Pre-renal azotemia and ATN are a spectrum of
manifestation of renal hypoperfusion
– 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

5. Acute Tubular Necrosis (ATN)
What segments of the nephron? Why?
How to recognize – clinical/histological
Pathophysiology
Ischemia/toxins
Clinical course

6. Acute Tubular Necrosis (ATN)
Site of tubular injury
• 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

10. Acute Tubular Necrosis (ATN)
Causes of cell injury
– Endothelin/Nitric Oxide balance
• Endothelin(ET-1 isoform) potent vasoconstrictor
produced in renal endothelium, epithelium, mesangium
• Nitric Oxide potent vasodilator produced in endothelium
– ATP Depletion
– Cell Swelling

11. Acute Tubular Necrosis (ATN)
Causes of cell injury
– Intracellular Calcium increases
– Intracellular acidosis
– Oxidant injury
– Inflammatory response from ischemia/reperfusion

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BY: DR RAI M. AMMAR MADNI

14. Acute Tubular Necrosis (ATN)
Tubular Injury
– Cell swelling, vacuolation, apical blebbing, loss of
brush border, loss of cell polarity, necrosis,
sloughing

16. Acute Tubular Necrosis (ATN)
Histopathology

17. Acute Tubular Necrosis (ATN)
Nephrotoxins
– Endogenous – myoglobin, hemoglobin, light
chains, Crystals, Hypercalcemia
– Exogenous – ethylene glycol, IV contrast,
Medications: Aminoglycosides, Acyclovir,
Methotrexate, Amphotericin B, Cisplatin,
Ifosfamide, Foscarnet

18. Acute Tubular Necrosis (ATN)
Clinical Course
– Initiation phase
– Maintenance phase
• GFR = 5-10 ml/min
• Lasts weeks to months
– Recovery phase
• Heralded by increase of urine output

19. Acute Tubular Necrosis (ATN)
Diagnostics
– FENA >1%
– Una > 40 Meq/dL
– Uosm < 350 mosm/dL
– Renal Ultrasound – normal size
– Urine microscopic – “muddy brown cast”

20. Acute Tubular Necrosis (ATN)
Outcomes
– Mortality about 50%

21. Acute Tubular Necrosis (ATN)
Treatment
– Supportive – maintain pt non-oliguric for ease in
fluid balance/management
– Maintain perfusion of kidneys MAP=65
– Treat underlying illness/interrupt insult

22. Acute Tubular Necrosis (ATN)
Review
– 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%

23. References
The Kidney 6th Edition, Brenner and Rector
Comprehensive Clinical Nephrology, Johnson
Clinical Physiology of Acid-Base and Electrolyte
Disorders, Rose

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www.twitter.com/drraiammar
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For Any Book or Notes Visit Our Website:
www.allmedicaldata.wordpress.com
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oR9V3OdFNTJW5yqXWXxA
BY: DR RAI M. AMMAR MADNI