What causes acute tubular necrosis (ATN)?

Causes of Acute Tubular Necrosis (ATN)

Acute tubular necrosis (ATN) is primarily caused by ischemia, nephrotoxins, or a combination of both factors (mixed etiology), with ischemic and mixed causes accounting for approximately 90% of all ATN cases. 1

Primary Etiologies

1. Ischemic ATN (51% of cases) 1

• Renal hypoperfusion conditions:
  • Hypovolemia (hemorrhage, severe dehydration, gastrointestinal bleeding)
  • Cardiogenic shock
  • Sepsis and septic shock
  • Severe hypotension
  • Prolonged warm ischemia during surgery (>25-30 minutes) 2
  • Major trauma
  • Burns

2. Nephrotoxic ATN (11% of cases) 1

• Exogenous toxins:

  • Medications:
    • Antibiotics (aminoglycosides, amphotericin B)
    • Chemotherapeutic agents
    • Contrast media
    • NSAIDs
    • ACE inhibitors/ARBs in susceptible patients
  • Heavy metals
  • Organic solvents

• Endogenous toxins:

  • Myoglobin (rhabdomyolysis)
  • Hemoglobin (hemolysis)
  • Uric acid (tumor lysis syndrome)
  • Light chains (multiple myeloma)

3. Mixed ATN (38% of cases) 1

• Combination of ischemic and nephrotoxic insults
• Common in critically ill patients receiving multiple nephrotoxic medications while experiencing hemodynamic instability
• Anticancer drug-related nephrotoxicity combined with other factors 2

Clinical Significance of ATN Etiology

The cause of ATN significantly impacts prognosis and outcomes:

• Mortality rates:

  • Nephrotoxic ATN: 38% 1
  • Ischemic ATN: 66% 1
  • Mixed ATN: 63% 1

• Renal recovery at discharge:

  • Nephrotoxic ATN: 100% of survivors 3
  • Ischemic ATN: 74% of survivors 3
  • Mixed ATN: 30% of survivors 3

Risk Factors and Contributing Conditions

• Pre-existing conditions:

  • Advanced age
  • Chronic kidney disease
  • Diabetes mellitus
  • Cirrhosis and liver disease 2
  • Malignancy
  • Heart failure

• Systemic factors:

  • Systemic inflammation 2
  • Adrenal dysfunction 2
  • Intra-abdominal hypertension 2
  • Hepatorenal reflex 2

• Iatrogenic factors:

  • Surgical procedures with renal ischemia
  • Tyrosine kinase inhibitors and other targeted therapies 2
  • Immune checkpoint inhibitors (causing autoimmune nephritis) 2

Prevention Strategies

• Maintaining adequate renal perfusion during high-risk procedures 4
• Proper hydration before contrast administration 4
• Dose adjustment of nephrotoxic medications 4
• Monitoring drug levels for potentially nephrotoxic agents 4
• Early recognition and treatment of sepsis and shock 4
• Avoiding nephrotoxins in high-risk patients 2
• Intraoperative measures to prevent ischemic injury:
  • Use of hypothermia
  • Early unclamping
  • Zero ischemia techniques 2

Understanding the specific cause of ATN is crucial for appropriate management and prognostication, as the three forms represent different patient populations with distinct clinical characteristics and outcomes 1.