Updated: 8/5/2020

Acute Tubular Necrosis

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Snapshot
  • A 52-year-old man with a past medical history of diabetes mellitus presents with fever and acute onset left lower quadrant abdominal pain. CT scan with contrast shows acute diverticulitis. He is started on broad-spectrum antibiotics. The next day, daily labs reveal a rise in creatinine from 0.7 mg/dL to 2.0 mg/dL. Urinalysis is obtained and a significant amount of muddy brown casts is found. He is immediately started on intravenous normal saline.
Introduction
  • Clinical definition
    • intrinsic acute kidney injury (AKI) to the kidneys from ischemia and/or toxins
  • Epidemiology
    • incidence
      • US incidence
        • most common cause of AKI in hospitalized patients
    • risk factors
      • pre-existing kidney disease
  • Etiology
    • ischemia
      • hypovolemia
      • sepsis
    • nephrotoxic injury
      • drugs
        • aminoglycosides
        • contrast for imaging
        • heavy metals
        • crystals
          • calcium oxalate crystals from ethylene glycol
          • urate crystals from tumor lysis syndrome
        • myoglobinuria
        • hemoglobinuria
  • Pathogenesis
    • decreased renal blood flow results in ischemia
      • this results in death of renal tubular cells
      • in particular the proximal convoluted tubule and thick ascending limb are affected
    • nephrotoxicity leads to damage in renal tubules
      • in particular proximal convoluted tubule is affected
  • Prognosis
    • 3 stages of disease
      • inciting event
      • oliguric (maintenance) phase
        • 1-3 week duration
        • risk of electrolyte abnormalities
          • hyperkalemia
          • metabolic acidosis
          • uremia
      • polyuric (recovery) phase
        • BUN and creatinine return back to normal
        • re-epithelialization of tubules
        • risk of hypokalemia
    • prognostic variable
      • negative
        • requiring dialysis
    • survival with treatment
      • over half of patients fully recover
      • 5-11% require long-term dialysis
        • 50% mortality in those needing dialysis
 
Classification of Acute Renal Failures
Urinary Indices Pre-Renal Intrinsic Renal Post-Renal
Urine osmolality (mOsm/kg)
  • > 500
  • < 350
  • < 350
Urine Na (mEq/L)
  • < 20
  • > 40
  • > 40
Serum BUN:creatinine
  • > 20
  • < 15
  • < 15
FENa (%)
(fractional excretion of Na)
  • < 1%
  • > 2%
  • > 2%
FEUrea (%) (fractional excretion of urea)
  • < 35%
  • 50-65 %
-
 
Presentation
  • Symptoms 
    • primary symptoms
      • signs of acute renal failure
        • vomit
        • diarrhea
        • blood loss
        • shock
        • altered mental status
      • oliguria or polyuria
  • Physical exam
    • signs of volume overload
      • edema
      • jugular venous distention
      • decreased breath sounds in pulmonary edema
Imaging
  • Ultrasound
    • indications
      • if an obstruction needs to be ruled out (post-renal cause of AKI)
      • best initial test
    • findings
      • can see hydronephrosis or stones
  • Histology
    • rarely obtained unless concerned about a concurrent glomerular process
      • will show necrosis of tubular lining cells 
Studies
  • Labs
    • serum potassium
      • hyperkalemia during oliguric phase
      • hypokalemia during polyuric phase
    • anion gap metabolic acidosis
    • ↑ BUN
    • ↑ creatinine
      • BUN:creatinine ratio < 15
  • Urinalysis with microscopy and sediment analysis
    • granular casts 
      • “muddy brown” from sloughing of tubular cells
  • Diagnostic criteria
    • diagnosis of AKI
      • ↑ serum creatinine of 0.3 mg/dL within 48 hours
      • ↑ serum creatinine of 1.5 fold from baseline
    • signs of acute tubular necrosis
      • urine osmolality < 350-500 mOsm/kg
      • muddy brown casts on urine sediment analysis
      • fractional excretion of sodium > 2%
      • decreased BUN:creatinine ratio
Differential
  • Prerenal azotemia
    • BUN:creatinine ratio > 20
  • Post-renal azotemia
    • source of obstruction found on imaging
      • e.g., stones or congenital abnormality
Treatment
  • Conservative
    • supportive care
      • remove nephrotoxic agent
      • intravenous hydration
      • close electrolyte and fluid level monitoring
      • indications
        • for all with suspected acute tubular necrosis
  • Medical
    • renal replacement therapy (dialysis)
      • indications
        • signs of fluid overload
        • toxic electrolyte levels
Complications
  • Electrolyte abnormalities
    • hypokalemia
    • hyperkalemia
  • Volume overload
 

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(M1.RL.13.5) A 40-year-old male presents to the emergency room following a motorcycle accident. His blood pressure on arrival is 70/50 mmHg and his heart rate is 130 bpm. During hospitalization, he developed oliguria and has urine studies shown in Figure A. He is eventually discharged from the hospital with restored renal function. Which of the following was responsible for this patient's kidney problems? Tested Concept

QID: 100959
FIGURES:
1

Acute pyelonephritis

3%

(1/36)

2

Diabetic glomerulopathy

0%

(0/36)

3

Rapidly progressive glomerulonephritis

11%

(4/36)

4

Acute tubular necrosis

81%

(29/36)

5

Membranous glomerulonephritis

3%

(1/36)

M 1 E

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(M1.RL.13.79) A 48-year-old woman is admitted to the hospital with sepsis and treated with gentamicin. One week after her admission, she develops oliguria and her urine shows muddy brown casts on light microscopy. Days later, her renal function begins to recover, but she complains of weakness and develops U waves on EKG as shown in Image A. Which laboratory abnormality would you most expect to see in this patient? Tested Concept

QID: 101033
FIGURES:
1

Hypocalcemia

5%

(2/42)

2

Hypokalemia

83%

(35/42)

3

Hyponatremia

2%

(1/42)

4

Hypoglycemia

0%

(0/42)

5

Hypermagnesemia

5%

(2/42)

M 2 D

Select Answer to see Preferred Response

(M1.RL.12.38) A 62-year-old man presents to the emergency room with an acute myocardial infarction. Twenty-four hours after admission to the cardiac intensive care unit, he develops oliguria. Laboratory tests show that his serum BUN is 59 mg/dL and his serum creatinine is 6.2 mg/dL. Renal biopsy reveals necrosis of the proximal tubules and thick ascending limb of Henle's loop. Which of the following would you most likely observe on a microscopic examination of this patient's urine? Tested Concept

QID: 100992
1

White blood cell casts

3%

(1/30)

2

Fatty casts

0%

(0/30)

3

Muddy brown casts

77%

(23/30)

4

Hyaline casts

3%

(1/30)

5

Broad waxy casts

13%

(4/30)

M 2 D

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