What is the most common cause of Acute Kidney Injury (AKI)?

Prerenal Azotemia is the Most Common Cause of AKI

Prerenal causes account for more than 60% of all acute kidney injury cases in general hospitalized patients, making prerenal azotemia the correct answer. 1, 2

Epidemiology of AKI Causes

The distribution of AKI etiologies follows a clear hierarchy:

• Prerenal causes dominate at >60% of cases, resulting from decreased renal perfusion without initial structural kidney damage 1, 2
• Intrarenal causes (primarily acute tubular necrosis) account for approximately 35% of cases in general hospitalized patients 1, 2
• Postrenal obstruction represents <3% of hospitalized AKI cases 1, 2
• Acute interstitial nephritis is an important but less common intrarenal cause compared to ATN 2

In the specific population of hospitalized patients with decompensated cirrhosis, prerenal AKI is even more dominant at approximately 68% of cases 1

Why Prerenal Azotemia Predominates

Prerenal AKI results from multiple common clinical scenarios that reduce renal perfusion:

Volume depletion mechanisms:

• Hemorrhage, gastrointestinal losses, burns, or excessive diuresis causing absolute volume depletion 1, 2
• Third-space fluid sequestration in pancreatitis or peritonitis 1, 2
• Severe hypoalbuminemia from nephrotic syndrome 1, 2

Hemodynamic compromise:

• Decreased cardiac output from heart failure, cardiogenic shock, or arrhythmias 1, 2
• Systemic vasodilation from sepsis, anaphylaxis, or cirrhosis 1, 2

Medication-related causes:

• NSAIDs, diuretics, and ACE inhibitors/ARBs that impair renal autoregulation 1, 2
• The "triple whammy" combination of NSAIDs, diuretics, and renin-angiotensin system inhibitors dramatically increases AKI risk 2

Clinical Significance of Acute Tubular Necrosis

While ATN is the second most common cause overall, it remains the most common intrinsic cause of AKI when prerenal causes are excluded 2, 3. ATN results from ischemic or nephrotoxic injury and carries significant long-term implications 4, 3. Patients with biopsy-proven ATN face a 12.14-fold higher risk of developing ESRD compared to controls 4, and the "maladaptive repair" phenomenon leads to accelerated renal aging and increased susceptibility to future nephrotoxicity 3.

Diagnostic Approach to Confirm Prerenal Etiology

The key to confirming prerenal AKI is demonstrating reversibility with volume repletion:

• Administer a fluid challenge with albumin at 1 g/kg (maximum 100 g/day) to differentiate prerenal from intrinsic causes 1
• Response to volume expansion is diagnostic: hypovolemic (prerenal) AKI shows reduction in serum creatinine to within 0.3 mg/dL of baseline 1
• BUN/creatinine ratio >20:1 suggests prerenal azotemia, while <15:1 suggests intrinsic kidney disease 2
• Fractional excretion of sodium (FENa) <1% suggests prerenal causes, though specificity is only 14% in cirrhosis 2
• Bland/normal urine sediment is highly suggestive of prerenal AKI 5

Common Pitfalls

Do not assume discrete categories: Traditional classification into prerenal, intrarenal, and postrenal is problematic because AKI is mostly multifactorial 5, 6. Sepsis, for instance, is a common precipitant that doesn't fit neatly into traditional categories 5.

Do not delay treatment while categorizing: When AKI is diagnosed, immediately discontinue diuretics and nephrotoxic medications (NSAIDs, ACE inhibitors/ARBs), treat the precipitating cause, and replace fluid losses 7, 5. In cirrhotic patients, all diuretics should be withdrawn regardless of AKI stage 7, 5.