What are the causes of acute kidney injury (AKI) azotemia?

Causes of Acute Kidney Injury Azotemia

Acute kidney injury (AKI) azotemia is primarily categorized into three major types: prerenal (60%), intrinsic renal, and postrenal causes, with prerenal and intrinsic renal etiologies accounting for >97% of all AKI cases. 1

Prerenal Causes

• Impaired renal blood flow from hypotension, hypovolemia, decreased cardiac output, or renal artery occlusion 1
• Volume depletion through various mechanisms:
  • Hemorrhage, excessive diuresis, gastrointestinal losses (vomiting, diarrhea)
  • Alcohol-induced diuresis, vomiting, and reduced fluid intake 2
  • Sequestration of fluids in third spaces (pancreatitis, peritonitis) 3
• Decreased effective circulating volume despite normal total body volume:
  • Congestive heart failure
  • Liver cirrhosis with portal hypertension
  • Nephrotic syndrome with severe hypoalbuminemia 3
• Vascular occlusion including renal artery thrombosis or embolism 3
• Medications that alter renal hemodynamics:
  • NSAIDs, ACE inhibitors, ARBs, especially when combined with diuretics (the "triple whammy" effect) 2

Intrinsic Renal Causes

• Acute tubular necrosis (ATN) from ischemia or nephrotoxins 1
• Nephrotoxic medications and substances:
  • Aminoglycosides causing direct tubular toxicity 4
  • Contrast media, especially in patients with pre-existing kidney disease 3
  • Chemotherapeutic agents
  • Heavy metals and organic solvents 5
• Pigment-induced injury from hemoglobin or myoglobin (rhabdomyolysis) 5
• Glomerular diseases including glomerulonephritis 1
• Interstitial nephritis often drug-induced 1
• Vascular diseases including vasculitis, thrombotic microangiopathies 1
• Renal infections or infiltrative processes 1

Postrenal Causes

• Urinary tract obstruction at any level:
  • Ureteral obstruction (stones, tumors, blood clots)
  • Bladder outlet obstruction (prostatic hypertrophy, neurogenic bladder)
  • Urethral obstruction 1

Special Considerations

Alcohol-Induced AKI

• Direct nephrotoxicity, rhabdomyolysis, volume depletion, and hepatorenal syndrome in patients with alcoholic liver disease 2
• Systemic inflammatory response syndrome (SIRS) in alcoholic hepatitis increases risk for AKI 2

Acute-on-Chronic Kidney Disease

• Patients with pre-existing CKD are at higher risk for developing AKI 1
• Percentage rises in creatinine may be curtailed in CKD, making detection of acute-on-chronic kidney injury more challenging 1
• Requires special attention as it carries significant mortality risk 1

Transient AKI

• Rapidly reversible form of AKI, related to prerenal azotemia 1
• Not benign - involves modest structural kidney injury and carries significant mortality (13-15% vs 3% in patients without AKI) 1, 6
• Represents about one-third of all AKI cases 1

Diagnostic Approach

• AKI is defined as an increase in creatinine by 0.3 mg/dL within 48 hours, an increase in serum creatinine to 1.5 times baseline within 7 days, or urine volume <0.5 mL/kg/hr for 6 hours 1
• Laboratory findings to differentiate causes:
  • BUN/creatinine ratio >20:1 suggests prerenal azotemia 3
  • Fractional excretion of sodium (FENa) <1% in prerenal causes 2
  • Fractional excretion of urea (FEUrea) <28.16% may better discriminate prerenal causes 2
  • Urinalysis showing casts, cells, or protein suggests intrinsic renal disease 1

Management Principles

• Identify and correct underlying cause of AKI 3
• Discontinue nephrotoxic medications when possible 3
• Restore appropriate volume status - fluid resuscitation for hypovolemia, avoiding fluid overload 3
• Monitor kidney function, electrolytes, and volume status closely 3
• Consider renal replacement therapy for severe cases (Stage 3 AKI) 1

Prevention Strategies

• Avoid nephrotoxic medications in high-risk patients 2
• Ensure adequate hydration, especially before contrast procedures 3
• Use low-osmolar or iso-osmolar contrast media when needed 3
• Follow-up evaluation 3 months after AKI episode to assess for resolution or progression to CKD 3