Acute Tubular Necrosis

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

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