Updated: 8/10/2018

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
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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Questions (6)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.RL.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? Review Topic

QID: 100959
FIGURES:
1

Acute pyelonephritis

0%

(0/12)

2

Diabetic glomerulopathy

0%

(0/12)

3

Rapidly progressive glomerulonephritis

0%

(0/12)

4

Acute tubular necrosis

92%

(11/12)

5

Membranous glomerulonephritis

8%

(1/12)

M1

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PREFERRED RESPONSE 4

(M1.RL.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? Review Topic

QID: 100992
1

White blood cell casts

0%

(0/8)

2

Fatty casts

0%

(0/8)

3

Muddy brown casts

88%

(7/8)

4

Hyaline casts

0%

(0/8)

5

Broad waxy casts

12%

(1/8)

M1

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PREFERRED RESPONSE 3

(M1.RL.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? Review Topic

QID: 101033
FIGURES:
1

Hypocalcemia

0%

(0/16)

2

Hypokalemia

94%

(15/16)

3

Hyponatremia

0%

(0/16)

4

Hypoglycemia

0%

(0/16)

5

Hypermagnesemia

0%

(0/16)

M1

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PREFERRED RESPONSE 2
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