Acute Tubular Necrosis

1
Acute Tubular Necrosis

• Douglas Stahura D.O.
• Grandview Hospital
• 7/24/2002

2
Causes of Acute Renal Failure

• Pre-renal
• Renal parenchymal (intrinsic)
• Post-renal

3
(No Transcript)
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

7
(No Transcript)
8
(No Transcript)
9
(No Transcript)
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

12
(No Transcript)
13
Acute Tubular Necrosis (ATN)

• Tubular Injury
• Cell swelling, vacuolation, apical blebbing, loss
  of brush border, loss of cell polarity, necrosis,
  sloughing

14
(No Transcript)
15
Acute Tubular Necrosis (ATN)Histopathology
16
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

17
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

18
Acute Tubular Necrosis (ATN)

• Diagnostics
• FENA gt1
• Una gt 40 Meq/dL
• Uosm lt 350 mosm/dL
• Renal Ultrasound normal size
• Urine microscopic muddy brown cast

19
Acute Tubular Necrosis (ATN)

• Outcomes
• Mortality about 50

20
Acute Tubular Necrosis (ATN)

• Treatment
• Supportive maintain pt non-oliguric for ease in
  fluid balance/management
• Maintain perfusion of kidneys MAP65
• Treat underlying illness/interrupt insult

21

• 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

22
References

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